1932

Abstract

The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein subunits, ∼110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures, combined with biochemical reconstitution experiments, cross-linking mass spectrometry, and cryo–electron tomography, has facilitated the determination of the near-atomic overall architecture of the symmetric core of the human, fungal, and algal NPCs. Here, we discuss the insights gained from these new advances and outstanding issues regarding NPC structure and function. The powerful combination of bottom-up and top-down approaches toward determining the structure of the NPC offers a paradigm for uncovering the architectures of other complex biological machines to near-atomic resolution.

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2019-06-20
2024-12-12
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Literature Cited

  1. 1. 
    Hoelz A, Debler EW, Blobel G 2011. The structure of the nuclear pore complex. Annu. Rev. Biochem. 80:613–43
    [Google Scholar]
  2. 2. 
    Watson ML. 1959. Further observations on the nuclear envelope of the animal cell. J. Biophys. Biochem. Cytol. 6:147–56
    [Google Scholar]
  3. 3. 
    Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT 2000. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148:635–51
    [Google Scholar]
  4. 4. 
    Ribbeck K, Görlich D. 2001. Kinetic analysis of translocation through nuclear pore complexes. EMBO J 20:1320–30
    [Google Scholar]
  5. 5. 
    Denning DP, Patel SS, Uversky V, Fink AL, Rexach M 2003. Disorder in the nuclear pore complex: The FG repeat regions of nucleoporins are natively unfolded. PNAS 100:2450–55
    [Google Scholar]
  6. 6. 
    Timney BL, Raveh B, Mironska R, Trivedi JM, Kim SJ et al. 2016. Simple rules for passive diffusion through the nuclear pore complex. J. Cell Biol. 215:57–76
    [Google Scholar]
  7. 7. 
    Bonner WM. 1975. Protein migration into nuclei. I. Frog oocyte nuclei in vivo accumulate microinjected histones, allow entry to small proteins, and exclude large proteins. J. Cell Biol. 64:421–30
    [Google Scholar]
  8. 8. 
    Paine PL, Moore LC, Horowitz SB 1975. Nuclear envelope permeability. Nature 254:109–14
    [Google Scholar]
  9. 9. 
    Yang W, Gelles J, Musser SM 2004. Imaging of single-molecule translocation through nuclear pore complexes. PNAS 101:12887–92
    [Google Scholar]
  10. 10. 
    Naim B, Zbaida D, Dagan S, Kapon R, Reich Z 2009. Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier. EMBO J 28:2697–705
    [Google Scholar]
  11. 11. 
    Frey S, Rees R, Schünemann J, Ng SC, Fünfgeld K et al. 2018. Surface properties determining passage rates of proteins through nuclear pores. Cell 174:202–17.e9
    [Google Scholar]
  12. 12. 
    Christie M, Chang CW, Róna G, Smith KM, Stewart AG et al. 2016. Structural biology and regulation of protein import into the nucleus. J. Mol. Biol. 428:2060–90
    [Google Scholar]
  13. 13. 
    Matsuura Y. 2016. Mechanistic insights from structural analyses of Ran-GTPase-driven nuclear export of proteins and RNAs. J. Mol. Biol. 428:2025–39
    [Google Scholar]
  14. 14. 
    Soniat M, Chook YM. 2015. Nuclear localization signals for four distinct karyopherin-β nuclear import systems. Biochem. J. 468:353–62
    [Google Scholar]
  15. 15. 
    Cook A, Bono F, Jinek M, Conti E 2007. Structural biology of nucleocytoplasmic transport. Annu. Rev. Biochem. 76:647–71
    [Google Scholar]
  16. 16. 
    Pumroy RA, Cingolani G. 2015. Diversification of importin-α isoforms in cellular trafficking and disease states. Biochem. J. 466:13–28
    [Google Scholar]
  17. 17. 
    Smith A, Brownawell A, Macara IG 1998. Nuclear import of Ran is mediated by the transport factor NTF2. Curr. Biol. 8:1403–6
    [Google Scholar]
  18. 18. 
    Ribbeck K, Lipowsky G, Kent HM, Stewart M, Görlich D 1998. NTF2 mediates nuclear import of Ran. EMBO J 17:6587–98
    [Google Scholar]
  19. 19. 
    Kalab P, Weis K, Heald R 2002. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295:2452–56
    [Google Scholar]
  20. 20. 
    von Appen A, Beck M 2016. Structure determination of the nuclear pore complex with three-dimensional cryo electron microscopy. J. Mol. Biol. 428:2001–10
    [Google Scholar]
  21. 21. 
    Schwartz TU. 2016. The structure inventory of the nuclear pore complex. J. Mol. Biol. 428:1986–2000
    [Google Scholar]
  22. 22. 
    Callan HG, Tomlin SG, Waddington CH 1950. Experimental studies on amphibian oocyte nuclei. I. Investigation of the structure of the nuclear membrane by means of the electron microscope. Proc. R. Soc. B Biol. Sci. 137:367–78
    [Google Scholar]
  23. 23. 
    Watson ML. 1955. The nuclear envelope: its structure and relation to cytoplasmic membranes. J. Biophys. Biochem. Cytol. 1:257–70
    [Google Scholar]
  24. 24. 
    Gall JG. 1967. Octagonal nuclear pores. J. Cell Biol. 32:391–99
    [Google Scholar]
  25. 25. 
    Hinshaw JE, Carragher BO, Milligan RA 1992. Architecture and design of the nuclear pore complex. Cell 69:1133–41
    [Google Scholar]
  26. 26. 
    Akey CW, Radermacher M. 1993. Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy. J. Cell Biol. 122:1–19
    [Google Scholar]
  27. 27. 
    Akey CW. 1995. Structural plasticity of the nuclear pore complex. J. Mol. Biol. 248:273–93
    [Google Scholar]
  28. 28. 
    Fahrenkrog B, Hurt EC, Aebi U, Panté N 1998. Molecular architecture of the yeast nuclear pore complex: localization of Nsp1p subcomplexes. J. Cell Biol. 143:577–88
    [Google Scholar]
  29. 29. 
    Kiseleva E, Goldberg MW, Allen TD, Akey CW 1998. Active nuclear pore complexes in Chironomus: visualization of transporter configurations related to mRNP export. J. Cell Sci. 111:223–36
    [Google Scholar]
  30. 30. 
    Yang Q, Rout MP, Akey CW 1998. Three-dimensional architecture of the isolated yeast nuclear pore complex: functional and evolutionary implications. Mol. Cell 1:223–34
    [Google Scholar]
  31. 31. 
    Beck M, Forster F, Ecke M, Plitzko JM, Melchior F et al. 2004. Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306:1387–90
    [Google Scholar]
  32. 32. 
    Maimon T, Elad N, Dahan I, Medalia O 2012. The human nuclear pore complex as revealed by cryo-electron tomography. Structure 20:998–1006
    [Google Scholar]
  33. 33. 
    Mosalaganti S, Kosinski J, Albert S, Schaffer M, Strenkert D et al. 2018. In situ architecture of the algal nuclear pore complex. Nat. Commun. 9:2361
    [Google Scholar]
  34. 34. 
    Stoffler D, Feja B, Fahrenkrog B, Walz J, Typke D, Aebi U 2003. Cryo-electron tomography provides novel insights into nuclear pore architecture: implications for nucleocytoplasmic transport. J. Mol. Biol. 328:119–30
    [Google Scholar]
  35. 35. 
    Beck M, Lucic V, Forster F, Baumeister W, Medalia O 2007. Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. Nature 449:611–15
    [Google Scholar]
  36. 36. 
    Kosinski J, Mosalaganti S, von Appen A, Teimer R, DiGuilio AL et al. 2016. Molecular architecture of the inner ring scaffold of the human nuclear pore complex. Science 352:363–65
    [Google Scholar]
  37. 37. 
    von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL et al. 2015. In situ structural analysis of the human nuclear pore complex. Nature 526:140–43
    [Google Scholar]
  38. 38. 
    Bui KH, von Appen A, DiGuilio AL, Ori A, Sparks L et al. 2013. Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155:1233–43
    [Google Scholar]
  39. 39. 
    Eibauer M, Pellanda M, Turgay Y, Dubrovsky A, Wild A, Medalia O 2015. Structure and gating of the nuclear pore complex. Nat. Commun. 6:7532
    [Google Scholar]
  40. 40. 
    Kim SJ, Fernandez-Martinez J, Nudelman I, Shi Y, Zhang W et al. 2018. Integrative structure and functional anatomy of a nuclear pore complex. Nature 555:475–82
    [Google Scholar]
  41. 41. 
    Lin DH, Stuwe T, Schilbach S, Rundlet EJ, Perriches T et al. 2016. Architecture of the symmetric core of the nuclear pore. Science 352:aaf1015
    [Google Scholar]
  42. 42. 
    Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ 2002. Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 158:915–27
    [Google Scholar]
  43. 43. 
    DeGrasse JA, DuBois KN, Devos D, Siegel TN, Sali A et al. 2009. Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor. Mol. Cell. Proteom. 8:2119–30
    [Google Scholar]
  44. 44. 
    Tamura K, Fukao Y, Iwamoto M, Haraguchi T, Hara-Nishimura I 2010. Identification and characterization of nuclear pore complex components in Arabidopsis thaliana. . Plant Cell 22:4084–97
    [Google Scholar]
  45. 45. 
    Neumann N, Lundin D, Poole AM 2010. Comparative genomic evidence for a complete nuclear pore complex in the last eukaryotic common ancestor. PLOS ONE 5:e13241
    [Google Scholar]
  46. 46. 
    Doye V, Hurt E. 1997. From nucleoporins to nuclear pore complexes. Curr. Opin. Cell Biol. 9:401–11
    [Google Scholar]
  47. 47. 
    Vasu SK, Forbes DJ. 2001. Nuclear pores and nuclear assembly. Curr. Opin. Cell Biol. 13:363–75
    [Google Scholar]
  48. 48. 
    Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J et al. 2007. Determining the architectures of macromolecular assemblies. Nature 450:683–94
    [Google Scholar]
  49. 49. 
    Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J et al. 2007. The molecular architecture of the nuclear pore complex. Nature 450:695–701
    [Google Scholar]
  50. 50. 
    Ori A, Banterle N, Iskar M, Andrés-Pons A, Escher C et al. 2013. Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines. Mol. Syst. Biol. 9:648
    [Google Scholar]
  51. 51. 
    Fernandez-Martinez J, Kim SJ, Shi Y, Upla P, Pellarin R et al. 2016. Structure and function of the nuclear pore complex cytoplasmic mRNA export platform. Cell 167:1215–28.e25
    [Google Scholar]
  52. 52. 
    Rajoo S, Vallotton P, Onischenko E, Weis K 2018. Stoichiometry and compositional plasticity of the yeast nuclear pore complex revealed by quantitative fluorescence microscopy. PNAS 115:E3969–77
    [Google Scholar]
  53. 53. 
    Davis LI, Blobel G. 1986. Identification and characterization of a nuclear pore complex protein. Cell 45:699–709
    [Google Scholar]
  54. 54. 
    Rout MP, Wente SR. 1994. Pores for thought: nuclear pore complex proteins. Trends Cell Biol 4:357–65
    [Google Scholar]
  55. 55. 
    Devos D, Dokudovskaya S, Williams R, Alber F, Eswar N et al. 2006. Simple fold composition and modular architecture of the nuclear pore complex. PNAS 103:2172–77
    [Google Scholar]
  56. 56. 
    Finlay DR, Meier E, Bradley P, Horecka J, Forbes DJ 1991. A complex of nuclear pore proteins required for pore function. J. Cell Biol. 114:169–83
    [Google Scholar]
  57. 57. 
    Grandi P, Doye V, Hurt EC 1993. Purification of NSP1 reveals complex formation with ‘GLFG’ nucleoporins and a novel nuclear pore protein NIC96. EMBO J 12:3061–71
    [Google Scholar]
  58. 58. 
    Siniossoglou S, Wimmer C, Rieger M, Doye V, Tekotte H et al. 1996. A novel complex of nucleoporins, which includes Sec13p and a Sec13p homolog, is essential for normal nuclear pores. Cell 84:265–75
    [Google Scholar]
  59. 59. 
    Lutzmann M, Kunze R, Buerer A, Aebi U, Hurt E 2002. Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBO J 21:387–97
    [Google Scholar]
  60. 60. 
    Berke IC, Boehmer T, Blobel G, Schwartz TU 2004. Structural and functional analysis of Nup133 domains reveals modular building blocks of the nuclear pore complex. J. Cell Biol. 167:591–97
    [Google Scholar]
  61. 61. 
    Hsia KC, Stavropoulos P, Blobel G, Hoelz A 2007. Architecture of a coat for the nuclear pore membrane. Cell 131:1313–26
    [Google Scholar]
  62. 62. 
    Boehmer T, Jeudy S, Berke IC, Schwartz TU 2008. Structural and functional studies of Nup107/Nup133 interaction and its implications for the architecture of the nuclear pore complex. Mol. Cell 30:721–31
    [Google Scholar]
  63. 63. 
    Brohawn SG, Leksa NC, Spear ED, Rajashankar KR, Schwartz TU 2008. Structural evidence for common ancestry of the nuclear pore complex and vesicle coats. Science 322:1369–73
    [Google Scholar]
  64. 64. 
    Debler EW, Ma Y, Seo HS, Hsia KC, Noriega TR et al. 2008. A fence-like coat for the nuclear pore membrane. Mol. Cell 32:815–26
    [Google Scholar]
  65. 65. 
    Brohawn SG, Schwartz TU. 2009. Molecular architecture of the Nup84–Nup145C–Sec13 edge element in the nuclear pore complex lattice. Nat. Struct. Mol. Biol. 16:1173–77
    [Google Scholar]
  66. 66. 
    Kampmann M, Blobel G. 2009. Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex. Nat. Struct. Mol. Biol. 16:782–88
    [Google Scholar]
  67. 67. 
    Leksa NC, Brohawn SG, Schwartz TU 2009. The structure of the scaffold nucleoporin Nup120 reveals a new and unexpected domain architecture. Structure 17:1082–91
    [Google Scholar]
  68. 68. 
    Nagy V, Hsia KC, Debler EW, Kampmann M, Davenport AM et al. 2009. Structure of a trimeric nucleoporin complex reveals alternate oligomerization states. PNAS 106:17693–98
    [Google Scholar]
  69. 69. 
    Seo HS, Ma Y, Debler EW, Wacker D, Kutik S et al. 2009. Structural and functional analysis of Nup120 suggests ring formation of the Nup84 complex. PNAS 106:14281–86
    [Google Scholar]
  70. 70. 
    Whittle JRR, Schwartz TU. 2009. Architectural nucleoporins Nup157/170 and Nup133 are structurally related and descend from a second ancestral element. J. Biol. Chem. 284:28442–52
    [Google Scholar]
  71. 71. 
    Bilokapic S, Schwartz TU. 2012. Molecular basis for Nup37 and ELY5/ELYS recruitment to the nuclear pore complex. PNAS 109:15241–46
    [Google Scholar]
  72. 72. 
    Liu X, Mitchell JM, Wozniak RW, Blobel G, Fan J 2012. Structural evolution of the membrane-coating module of the nuclear pore complex. PNAS 109:16498–503
    [Google Scholar]
  73. 73. 
    Bilokapic S, Schwartz TU. 2013. Structural and functional studies of the 252 kDa nucleoporin ELYS reveal distinct roles for its three tethered domains. Structure 21:572–80
    [Google Scholar]
  74. 74. 
    Kim SJ, Fernandez-Martinez J, Sampathkumar P, Martel A, Matsui T et al. 2014. Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex. Mol. Cell. Proteom. 13:2911–26
    [Google Scholar]
  75. 75. 
    Kelley K, Knockenhauer KE, Kabachinski G, Schwartz TU 2015. Atomic structure of the Y complex of the nuclear pore. Nat. Struct. Mol. Biol. 22:425–31
    [Google Scholar]
  76. 76. 
    Stuwe T, Correia AR, Lin DH, Paduch M, Lu VT et al. 2015. Architecture of the nuclear pore complex coat. Science 347:1148–52
    [Google Scholar]
  77. 77. 
    Fontoura BMA, Blobel G, Matunis MJ 1999. A conserved biogenesis pathway for nucleoporins: Proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J. Cell Biol. 144:1097–112
    [Google Scholar]
  78. 78. 
    Belgareh N, Rabut G, Bai SW, van Overbeek M, Beaudouin J et al. 2001. An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. J. Cell Biol. 154:1147–60
    [Google Scholar]
  79. 79. 
    Franz C, Wázak R, Yavuz S, Santarella R, Gentzel M et al. 2007. MEL-28/ELYS is required for the recruitment of nucleoporins to chromatin and postmitotic nuclear pore complex assembly. EMBO Rep 8:165–72
    [Google Scholar]
  80. 80. 
    Rasala BA, Orjalo AV, Shen Z, Briggs S, Forbes DJ 2006. ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. PNAS 103:17801–6
    [Google Scholar]
  81. 81. 
    Loiodice I, Alves A, Rabut G, Van Overbeek M, Ellenberg J et al. 2004. The entire Nup107–160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Mol. Biol. Cell 15:3333–44
    [Google Scholar]
  82. 82. 
    Thierbach K, von Appen A, Thoms M, Beck M, Flemming D, Hurt E 2013. Protein interfaces of the conserved Nup84 complex from Chaetomium thermophilum shown by crosslinking mass spectrometry and electron microscopy. Structure 21:1672–82
    [Google Scholar]
  83. 83. 
    Stagg SM, LaPointe P, Balch WE 2007. Structural design of cage and coat scaffolds that direct membrane traffic. Curr. Opin. Struct. Biol. 17:221–28
    [Google Scholar]
  84. 84. 
    Whittle JRR, Schwartz TU. 2010. Structure of the Sec13–Sec16 edge element, a template for assembly of the COPII vesicle coat. J. Cell Biol. 190:347–61
    [Google Scholar]
  85. 85. 
    Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA et al. 2013. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340:1100–6
    [Google Scholar]
  86. 86. 
    Dokudovskaya S, Waharte F, Schlessinger A, Pieper U, Devos DP et al. 2011. A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae. Mol. Cell. Proteom 10: mcp.M110 006478
    [Google Scholar]
  87. 87. 
    Siniossoglou S, Lutzmann M, Santos-Rosa H, Leonard K, Mueller S et al. 2000. Structure and assembly of the Nup84p complex. J. Cell Biol. 149:41–54
    [Google Scholar]
  88. 88. 
    Sampathkumar P, Gheyi T, Miller SA, Bain KT, Dickey M et al. 2011. Structure of the C-terminal domain of Saccharomyces cerevisiae Nup133, a component of the nuclear pore complex. Proteins 79:1672–77
    [Google Scholar]
  89. 89. 
    Jeudy S, Schwartz TU. 2007. Crystal structure of nucleoporin Nic96 reveals a novel, intricate helical domain architecture. J. Biol. Chem. 282:34904–12
    [Google Scholar]
  90. 90. 
    Schrader N, Stelter P, Flemming D, Kunze R, Hurt E, Vetter IR 2008. Structural basis of the nic96 subcomplex organization in the nuclear pore channel. Mol. Cell 29:46–55
    [Google Scholar]
  91. 91. 
    Debler EW, Hsia KC, Nagy V, Seo HS, Hoelz A 2010. Characterization of the membrane-coating Nup84 complex: paradigm for the nuclear pore complex structure. Nucleus 1:150–57
    [Google Scholar]
  92. 92. 
    Devos D, Dokudovskaya S, Alber F, Williams R, Chait BT et al. 2004. Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PLOS Biol 2:e380
    [Google Scholar]
  93. 93. 
    Seo HS, Blus BJ, Jankovic NZ, Blobel G 2013. Structure and nucleic acid binding activity of the nucleoporin Nup157. PNAS 110:16450–55
    [Google Scholar]
  94. 94. 
    Drin G, Casella JF, Gautier R, Boehmer T, Schwartz TU, Antonny B 2007. A general amphipathic α-helical motif for sensing membrane curvature. Nat. Struct. Mol. Biol. 14:138–46
    [Google Scholar]
  95. 95. 
    Liu HL, De Souza CPC, Osmani AH, Osmani SA 2009. The three fungal transmembrane nuclear pore complex proteins of Aspergillus nidulans are dispensable in the presence of an intact An-Nup84-120 complex. Mol. Biol. Cell 20:616–30
    [Google Scholar]
  96. 96. 
    Rasala BA, Ramos C, Harel A, Forbes DJ 2008. Capture of AT-rich chromatin by ELYS recruits POM121 and NDC1 to initiate nuclear pore assembly. Mol. Biol. Cell 19:3982–96
    [Google Scholar]
  97. 97. 
    Xu C, Li Z, He H, Wernimont A, Li Y et al. 2015. Crystal structure of human nuclear pore complex component NUP43. FEBS Lett 589:3247–53
    [Google Scholar]
  98. 98. 
    Stuwe T, Bley CJ, Thierbach K, Petrovic S, Schilbach S et al. 2015. Architecture of the fungal nuclear pore inner ring complex. Science 350:56–64
    [Google Scholar]
  99. 99. 
    Stuwe T, Lin DH, Collins LN, Hurt E, Hoelz A 2014. Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins. PNAS 111:2530–35
    [Google Scholar]
  100. 100. 
    Amlacher S, Sarges P, Flemming D, van Noort V, Kunze R et al. 2011. Insight into structure and assembly of the nuclear pore complex by utilizing the genome of a eukaryotic thermophile. Cell 146:277–89
    [Google Scholar]
  101. 101. 
    Fischer J, Teimer R, Amlacher S, Kunze R, Hurt E 2015. Linker Nups connect the nuclear pore complex inner ring with the outer ring and transport channel. Nat. Struct. Mol. Biol. 22:774–81
    [Google Scholar]
  102. 102. 
    Hodel AE, Hodel MR, Griffis ER, Hennig KA, Ratner GA et al. 2002. The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98. Mol. Cell 10:347–58
    [Google Scholar]
  103. 103. 
    Handa N, Kukimoto-Niino M, Akasaka R, Kishishita S, Murayama K et al. 2006. The crystal structure of mouse Nup35 reveals atypical RNP motifs and novel homodimerization of the RRM domain. J. Mol. Biol. 363:114–24
    [Google Scholar]
  104. 104. 
    Sun Y, Guo HC. 2008. Structural constraints on autoprocessing of the human nucleoporin Nup98. Protein Sci 17:494–505
    [Google Scholar]
  105. 105. 
    Sampathkumar P, Kim SJ, Manglicmot D, Bain KT, Gilmore J et al. 2012. Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast. Candida glabrata. Proteins 80:2110–16
    [Google Scholar]
  106. 106. 
    Andersen KR, Onischenko E, Tang JH, Kumar P, Chen JZ et al. 2013. Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors. eLife 2:e00745
    [Google Scholar]
  107. 107. 
    Sampathkumar P, Kim SJ, Upla P, Rice WJ, Phillips J et al. 2013. Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex. Structure 21:560–71
    [Google Scholar]
  108. 108. 
    Mansfeld J, Guttinger S, Hawryluk-Gara LA, Panté N, Mall M et al. 2006. The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells. Mol. Cell 22:93–103
    [Google Scholar]
  109. 109. 
    Hawryluk-Gara LA, Platani M, Santarella R, Wozniak RW, Mattaj IW 2008. Nup53 is required for nuclear envelope and nuclear pore complex assembly. Mol. Biol. Cell 19:1753–62
    [Google Scholar]
  110. 110. 
    Onischenko E, Stanton LH, Madrid AS, Kieselbach T, Weis K 2009. Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance. J. Cell Biol. 185:475–91
    [Google Scholar]
  111. 111. 
    Eisenhardt N, Redolfi J, Antonin W 2014. Interaction of Nup53 with Ndc1 and Nup155 is required for nuclear pore complex assembly. J. Cell Sci. 127:908–21
    [Google Scholar]
  112. 112. 
    Vollmer B, Schooley A, Sachdev R, Eisenhardt N, Schneider AM et al. 2012. Dimerization and direct membrane interaction of Nup53 contribute to nuclear pore complex assembly. EMBO J 31:4072–84
    [Google Scholar]
  113. 113. 
    Chug H, Trakhanov S, Hülsmann BB, Pleiner T, Görlich D 2015. Crystal structure of the metazoan Nup62ċNup58ċNup54 nucleoporin complex. Science 350:106–10
    [Google Scholar]
  114. 114. 
    Andrade MA, Petosa C, O'Donoghue SI, Muller CW, Bork P 2001. Comparison of ARM and HEAT protein repeats. J. Mol. Biol. 309:1–18
    [Google Scholar]
  115. 115. 
    Flemming D, Devos DP, Schwarz J, Amlacher S, Lutzmann M, Hurt E 2012. Analysis of the yeast nucleoporin Nup188 reveals a conserved S-like structure with similarity to karyopherins. J. Struct. Biol. 177:99–105
    [Google Scholar]
  116. 116. 
    Theerthagiri G, Eisenhardt N, Schwarz H, Antonin W 2010. The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex. J. Cell Biol. 189:1129–42
    [Google Scholar]
  117. 117. 
    Rosenblum JS, Blobel G. 1999. Autoproteolysis in nucleoporin biogenesis. PNAS 96:11370–75
    [Google Scholar]
  118. 118. 
    Teixeira MT, Fabre E, Dujon B 1999. Self-catalyzed cleavage of the yeast nucleoporin Nup145p precursor. J. Biol. Chem. 274:32439–44
    [Google Scholar]
  119. 119. 
    Emtage JL, Bucci M, Watkins JL, Wente SR 1997. Defining the essential functional regions of the nucleoporin Nup145p. J. Cell Sci. 110:911–25
    [Google Scholar]
  120. 120. 
    Teixeira MT, Siniossoglou S, Podtelejnikov S, Bénichou JC, Mann M et al. 1997. Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins. EMBO J 16:5086–97
    [Google Scholar]
  121. 121. 
    Griffis ER, Xu S, Powers MA 2003. Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Mol. Biol. Cell 14:600–10
    [Google Scholar]
  122. 122. 
    Stuwe T, von Borzyskowski LS, Davenport AM, Hoelz A 2012. Molecular basis for the anchoring of proto-oncoprotein Nup98 to the cytoplasmic face of the nuclear pore complex. J. Mol. Biol. 419:330–46
    [Google Scholar]
  123. 123. 
    Sampathkumar P, Ozyurt SA, Do J, Bain KT, Dickey M et al. 2010. Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145. Proteins 78:1992–98
    [Google Scholar]
  124. 124. 
    Laurell E, Beck K, Krupina K, Theerthagiri G, Bodenmiller B et al. 2011. Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell 144:539–50
    [Google Scholar]
  125. 125. 
    Wente SR, Rout MP, Blobel G 1992. A new family of yeast nuclear pore complex proteins. J. Cell Biol. 119:705–23
    [Google Scholar]
  126. 126. 
    Yoshida K, Seo HS, Debler EW, Blobel G, Hoelz A 2011. Structural and functional analysis of an essential nucleoporin heterotrimer on the cytoplasmic face of the nuclear pore complex. PNAS 108:16571–76
    [Google Scholar]
  127. 127. 
    Strawn LA, Shen T, Shulga N, Goldfarb DS, Wente SR 2004. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat. Cell Biol. 6:197–206
    [Google Scholar]
  128. 128. 
    Kita K, Omata S, Horigome T 1993. Purification and characterization of a nuclear pore glycoprotein complex containing p62. J. Biochem. 113:377–82
    [Google Scholar]
  129. 129. 
    Guan T, Muller S, Klier G, Panté N, Blevitt JM et al. 1995. Structural analysis of the p62 complex, an assembly of O-linked glycoproteins that localizes near the central gated channel of the nuclear pore complex. Mol. Biol. Cell 6:1591–603
    [Google Scholar]
  130. 130. 
    Solmaz SR, Blobel G, Melcak I 2013. Ring cycle for dilating and constricting the nuclear pore. PNAS 110:5858–63
    [Google Scholar]
  131. 131. 
    Solmaz SR, Chauhan R, Blobel G, Melcak I 2011. Molecular architecture of the transport channel of the nuclear pore complex. Cell 147:590–602
    [Google Scholar]
  132. 132. 
    Melcak I, Hoelz A, Blobel G 2007. Structure of Nup58/45 suggests flexible nuclear pore diameter by intermolecular sliding. Science 315:1729–32
    [Google Scholar]
  133. 133. 
    Ulrich A, Partridge JR, Schwartz TU 2014. The stoichiometry of the nucleoporin 62 subcomplex of the nuclear pore in solution. Mol. Biol. Cell 25:1484–92
    [Google Scholar]
  134. 134. 
    Sharma A, Solmaz SR, Blobel G, Melcak I 2015. Ordered regions of channel nucleoporins Nup62, Nup54, and Nup58 form dynamic complexes in solution. J. Biol. Chem. 290:18370–78
    [Google Scholar]
  135. 135. 
    Koh J, Blobel G. 2015. Allosteric regulation in gating the central channel of the nuclear pore complex. Cell 161:1361–73
    [Google Scholar]
  136. 136. 
    Dewangan PS, Sonawane PJ, Chouksey AR, Chauhan R 2017. The Nup62 coiled-coil motif provides plasticity for triple-helix bundle formation. Biochemistry 56:2803–11
    [Google Scholar]
  137. 137. 
    Stavru F, Hülsmann BB, Spang A, Hartmann E, Cordes VC, Görlich D 2006. NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes. J. Cell Biol. 173:509–19
    [Google Scholar]
  138. 138. 
    Chial HJ, Rout MP, Giddings TH, Winey M 1998. Saccharomyces cerevisiae Ndc1p is a shared component of nuclear pore complexes and spindle pole bodies. J. Cell Biol. 143:1789–800
    [Google Scholar]
  139. 139. 
    Chadrin A, Hess B, San Roman M, Gatti X, Lombard B et al. 2010. Pom33, a novel transmembrane nucleoporin required for proper nuclear pore complex distribution. J. Cell Biol. 189:795–811
    [Google Scholar]
  140. 140. 
    Gerace L, Ottaviano Y, Kondor-Koch C 1982. Identification of a major polypeptide of the nuclear pore complex. J. Cell Biol. 95:826–37
    [Google Scholar]
  141. 141. 
    Hallberg E, Wozniak RW, Blobel G 1993. An integral membrane protein of the pore membrane domain of the nuclear envelope contains a nucleoporin-like region. J. Cell Biol. 122:513–21
    [Google Scholar]
  142. 142. 
    Wozniak RW, Bartnik E, Blobel G 1989. Primary structure analysis of an integral membrane glycoprotein of the nuclear pore. J. Cell Biol. 108:2083–92
    [Google Scholar]
  143. 143. 
    Wozniak RW, Blobel G, Rout MP 1994. POM152 is an integral protein of the pore membrane domain of the yeast nuclear envelope. J. Cell Biol. 125:31–42
    [Google Scholar]
  144. 144. 
    Hao Q, Zhang B, Yuan K, Shi H, Blobel G 2018. Electron microscopy of Chaetomium pom152 shows the assembly of ten-bead string. Cell Discov 4:56
    [Google Scholar]
  145. 145. 
    Upla P, Kim SJ, Sampathkumar P, Dutta K, Cahill SM et al. 2017. Molecular architecture of the major membrane ring component of the nuclear pore complex. Structure 25:434–45
    [Google Scholar]
  146. 146. 
    Hülsmann BB, Labokha AA, Görlich D 2012. The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model. Cell 150:738–51
    [Google Scholar]
  147. 147. 
    Walde S, Kehlenbach RH. 2010. The part and the whole: functions of nucleoporins in nucleocytoplasmic transport. Trends Cell Biol 20:461–69
    [Google Scholar]
  148. 148. 
    Schmidt HB, Görlich D. 2016. Transport selectivity of nuclear pores, phase separation, and membraneless organelles. Trends Biochem. Sci. 41:46–61
    [Google Scholar]
  149. 149. 
    Lim RYH, Huang B, Kapinos LE 2015. How to operate a nuclear pore complex by Kap-centric control. Nucleus 6:366–72
    [Google Scholar]
  150. 150. 
    Frey S, Görlich D. 2007. A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell 130:512–23
    [Google Scholar]
  151. 151. 
    Sakiyama Y, Mazur A, Kapinos LE, Lim RYH 2016. Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy. Nat. Nanotechnol. 11:719–23
    [Google Scholar]
  152. 152. 
    Adams RL, Terry LJ, Wente SR 2015. A novel Saccharomyces cerevisiae FG nucleoporin mutant collection for use in nuclear pore complex functional experiments. G3 Genes Genomes Genet 6:51–58
    [Google Scholar]
  153. 153. 
    Fiserova J, Richards SA, Wente SR, Goldberg MW 2010. Facilitated transport and diffusion take distinct spatial routes through the nuclear pore complex. J. Cell Sci. 123:2773–80
    [Google Scholar]
  154. 154. 
    Terry LJ, Wente SR. 2009. Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot. Cell 8:1814–27
    [Google Scholar]
  155. 155. 
    Onischenko E, Tang JH, Andersen KR, Knockenhauer KE, Vallotton P et al. 2017. Natively unfolded FG repeats stabilize the structure of the nuclear pore complex. Cell 171:904–17.e19
    [Google Scholar]
  156. 156. 
    Lutzmann M, Kunze R, Stangl K, Stelter P, Toth KF et al. 2005. Reconstitution of Nup157 and Nup145N into the Nup84 complex. J. Biol. Chem. 280:18442–51
    [Google Scholar]
  157. 157. 
    Faini M, Beck R, Wieland FT, Briggs JA 2013. Vesicle coats: structure, function, and general principles of assembly. Trends Cell Biol 23:279–88
    [Google Scholar]
  158. 158. 
    Vollmer B, Lorenz M, Moreno-Andrés D, Bodenhöfer M, De Magistris P et al. 2015. Nup153 recruits the Nup107–160 complex to the inner nuclear membrane for interphasic nuclear pore complex assembly. Dev. Cell 33:717–28
    [Google Scholar]
  159. 159. 
    Meszaros N, Cibulka J, Mendiburo MJ, Romanauska A, Schneider M, Köhler A 2015. Nuclear pore basket proteins are tethered to the nuclear envelope and can regulate membrane curvature. Dev. Cell 33:285–98
    [Google Scholar]
  160. 160. 
    Dawson TR, Lazarus MD, Hetzer MW, Wente SR 2009. ER membrane–bending proteins are necessary for de novo nuclear pore formation. J. Cell Biol. 184:659–75
    [Google Scholar]
  161. 161. 
    Yewdell WT, Colombi P, Makhnevych T, Lusk CP 2011. Lumenal interactions in nuclear pore complex assembly and stability. Mol. Biol. Cell 22:1375–88
    [Google Scholar]
  162. 162. 
    Webster BM, Colombi P, Jäger J, Lusk CP 2014. Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4. Cell 159:388–401
    [Google Scholar]
  163. 163. 
    Casey AK, Chen S, Novick P, Ferro-Novick S, Wente SR 2015. Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum. Mol. Biol. Cell 26:2833–44
    [Google Scholar]
  164. 164. 
    Webster BM, Thaller DJ, Jäger J, Ochmann SE, Borah S, Lusk CP 2016. Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing. EMBO J 35:2447–67
    [Google Scholar]
  165. 165. 
    Jarnik M, Aebi U. 1991. Toward a more complete 3-D structure of the nuclear pore complex. J. Struct. Biol. 107:291–308
    [Google Scholar]
  166. 166. 
    Hodge CA, Tran EJ, Noble KN, Alcázar-Román AR, Ben-Yishay R et al. 2011. The Dbp5 cycle at the nuclear pore complex during mRNA export I: dbp5 mutants with defects in RNA binding and ATP hydrolysis define key steps for Nup159 and Gle1. Genes Dev 25:1052–64
    [Google Scholar]
  167. 167. 
    Walther TC, Pickersgill HS, Cordes VC, Goldberg MW, Allen TD et al. 2002. The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J. Cell. Biol. 158:63–77
    [Google Scholar]
  168. 168. 
    Kiseleva E, Allen TD, Rutherford S, Bucci M, Wente SR, Goldberg MW 2004. Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments. J. Struct. Biol. 145:272–88
    [Google Scholar]
  169. 169. 
    Napetschnig J, Kassube SA, Debler EW, Wong RW, Blobel G, Hoelz A 2009. Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19. PNAS 106:3089–94
    [Google Scholar]
  170. 170. 
    Napetschnig J, Blobel G, Hoelz A 2007. Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN. PNAS 104:1783–88
    [Google Scholar]
  171. 171. 
    Ren Y, Seo HS, Blobel G, Hoelz A 2010. Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1. PNAS 107:10406–11
    [Google Scholar]
  172. 172. 
    Weirich CS, Erzberger JP, Berger JM, Weis K 2004. The N-terminal domain of Nup159 forms a β-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. Mol. Cell 16:749–60
    [Google Scholar]
  173. 173. 
    von Moeller H, Basquin C, Conti E 2009. The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner. Nat. Struct. Mol. Biol. 16:247–54
    [Google Scholar]
  174. 174. 
    Montpetit B, Thomsen ND, Helmke KJ, Seeliger MA, Berger JM, Weis K 2011. A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export. Nature 472:238–42
    [Google Scholar]
  175. 175. 
    Romes EM, Tripathy A, Slep KC 2012. Structure of a yeast Dyn2-Nup159 complex and molecular basis for dynein light chain–nuclear pore interaction. J. Biol. Chem. 287:15862–73
    [Google Scholar]
  176. 176. 
    Quan B, Seo HS, Blobel G, Ren Y 2014. Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1ċNup98). PNAS 111:9127–32
    [Google Scholar]
  177. 177. 
    Lin DH, Correia AR, Cai SW, Huber FM, Jette CA, Hoelz A 2018. Structural and functional analysis of mRNA export regulation by the nuclear pore complex. Nat. Commun. 9:2319
    [Google Scholar]
  178. 178. 
    Teimer R, Kosinski J, von Appen A, Beck M, Hurt E 2017. A short linear motif in scaffold Nup145C connects Y-complex with pre-assembled outer ring Nup82 complex. Nat. Commun. 8:1107
    [Google Scholar]
  179. 179. 
    Gaik M, Flemming D, von Appen A, Kastritis P, Mucke N et al. 2015. Structural basis for assembly and function of the Nup82 complex in the nuclear pore scaffold. J. Cell Biol. 208:283–97
    [Google Scholar]
  180. 180. 
    Belgareh N, Snay-Hodge C, Pasteau F, Dagher S, Cole CN, Doye V 1998. Functional characterization of a Nup159p-containing nuclear pore subcomplex. Mol. Biol. Cell 9:3475–92
    [Google Scholar]
  181. 181. 
    Bailer SM, Balduf C, Hurt E 2001. The Nsp1p carboxy-terminal domain is organized into functionally distinct coiled-coil regions required for assembly of nucleoporin subcomplexes and nucleocytoplasmic transport. Mol. Cell. Biol. 21:7944–55
    [Google Scholar]
  182. 182. 
    Bailer SM, Balduf C, Katahira J, Podtelejnikov A, Rollenhagen C et al. 2000. Nup116p associates with the Nup82p-Nsp1p-Nup159p nucleoporin complex. J. Biol. Chem. 275:23540–48
    [Google Scholar]
  183. 183. 
    Pritchard CE, Fornerod M, Kasper LH, van Deursen JM 1999. RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains. J. Cell Biol. 145:237–54
    [Google Scholar]
  184. 184. 
    Bailer SM, Siniossoglou S, Podtelejnikov A, Hellwig A, Mann M, Hurt E 1998. Nup116p and Nup100p are interchangeable through a conserved motif which constitutes a docking site for the mRNA transport factor Gle2p. EMBO J 17:1107–19
    [Google Scholar]
  185. 185. 
    Blevins MB, Smith AM, Phillips EM, Powers MA 2003. Complex formation among the RNA export proteins Nup98, Rae1/Gle2, and TAP. J. Biol. Chem. 278:20979–88
    [Google Scholar]
  186. 186. 
    Murphy R, Watkins JL, Wente SR 1996. GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function. Mol. Biol. Cell 7:1921–37
    [Google Scholar]
  187. 187. 
    Stutz F, Neville M, Rosbash M 1995. Identification of a novel nuclear pore–associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell 82:495–506
    [Google Scholar]
  188. 188. 
    Watkins JL, Murphy R, Emtage JL, Wente SR 1998. The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export. PNAS 95:6779–84
    [Google Scholar]
  189. 189. 
    Hodge CA, Colot HV, Stafford P, Cole CN 1999. Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1-1 cells. EMBO J 18:5778–88
    [Google Scholar]
  190. 190. 
    Strahm Y, Fahrenkrog B, Zenklusen D, Rychner E, Kantor J et al. 1999. The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG-nucleoporin Rip1p, the DEAD-box protein Rat8p/Dbp5p and a new protein Ymr 255p. EMBO J 18:5761–77
    [Google Scholar]
  191. 191. 
    Sloan KE, Bohnsack MT. 2018. Unravelling the mechanisms of RNA helicase regulation. Trends Biochem. Sci. 43:237–50
    [Google Scholar]
  192. 192. 
    Rayala HJ, Kendirgi F, Barry DM, Majerus PW, Wente SR 2004. The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155. Mol. Cell. Proteom. 3:145–55
    [Google Scholar]
  193. 193. 
    Kendirgi F, Rexer DJ, Alcázar-Román AR, Onishko HM, Wente SR 2005. Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin hCG1: a conserved mechanism in the export of Hsp70 mRNA. Mol. Biol. Cell 16:4304–15
    [Google Scholar]
  194. 194. 
    Folkmann AW, Collier SE, Zhan X, Aditi Ohi MD, Wente SR 2013. Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease. Cell 155:582–93
    [Google Scholar]
  195. 195. 
    Alcázar-Román AR, Tran EJ, Guo S, Wente SR 2006. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nat. Cell Biol. 8:711–16
    [Google Scholar]
  196. 196. 
    Weirich CS, Erzberger JP, Flick JS, Berger JM, Thorner J, Weis K 2006. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nat. Cell Biol. 8:668–76
    [Google Scholar]
  197. 197. 
    Adams RL, Mason AC, Glass L, Aditi Wente SR 2017. Nup42 and IP6 coordinate Gle1 stimulation of Dbp5/DDX19B for mRNA export in yeast and human cells. Traffic 18:776–90
    [Google Scholar]
  198. 198. 
    Schmitt C, von Kobbe C, Bachi A, Panté N, Rodrigues JP et al. 1999. Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p. EMBO J 18:4332–47
    [Google Scholar]
  199. 199. 
    Stelter P, Kunze R, Flemming D, Hopfner D, Diepholz M et al. 2007. Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex. Nat. Cell Biol. 9:788–96
    [Google Scholar]
  200. 200. 
    Kellner N, Schwarz J, Sturm M, Fernandez-Martinez J, Griesel S et al. 2016. Developing genetic tools to exploit Chaetomium thermophilum for biochemical analyses of eukaryotic macromolecular assemblies. Sci. Rep. 6:20937
    [Google Scholar]
  201. 201. 
    Kim DI, Birendra KC, Zhu W, Motamedchaboki K, Doye V, Roux KJ 2014. Probing nuclear pore complex architecture with proximity-dependent biotinylation. PNAS 111:E2453–61
    [Google Scholar]
  202. 202. 
    Clouse KN, Luo MJ, Zhou Z, Reed R 2001. A Ran-independent pathway for export of spliced mRNA. Nat. Cell Biol. 3:97–99
    [Google Scholar]
  203. 203. 
    Lund MK, Guthrie C. 2005. The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim. Mol. Cell 20:645–51
    [Google Scholar]
  204. 204. 
    Linder P, Jankowsky E. 2011. From unwinding to clamping—the DEAD box RNA helicase family. Nat. Rev. Mol. Cell Biol. 12:505–16
    [Google Scholar]
  205. 205. 
    Collins R, Karlberg T, Lehtiö L, Schütz P, van den Berg S et al. 2009. The DEXD/H-box RNA helicase DDX19 is regulated by an α-helical switch. J. Biol. Chem. 284:10296–300
    [Google Scholar]
  206. 206. 
    Folkmann AW, Noble KN, Cole CN, Wente SR 2011. Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. Nucleus 2:540–48
    [Google Scholar]
  207. 207. 
    Wong EV, Gray S, Cao W, Montpetit R, Montpetit B, De La Cruz EM 2018. Nup159 weakens Gle1 binding to Dbp5 but does not accelerate ADP release. J. Mol. Biol. 430:2080–95
    [Google Scholar]
  208. 208. 
    Noble KN, Tran EJ, Alcázar-Román AR, Hodge CA, Cole CN, Wente SR 2011. The Dbp5 cycle at the nuclear pore complex during mRNA export II: Nucleotide cycling and mRNP remodeling by Dbp5 are controlled by Nup159 and Gle1. Genes Dev 25:1065–77
    [Google Scholar]
  209. 209. 
    Wong EV, Cao W, Vörös J, Merchant M, Modis Y et al. 2016. Pi release limits the intrinsic and RNA-stimulated ATPase cycles of DEAD-box protein 5 (Dbp5). J. Mol. Biol. 428:492–508
    [Google Scholar]
  210. 210. 
    Wu J, Matunis MJ, Kraemer D, Blobel G, Coutavas E 1995. Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. J. Biol. Chem. 270:14209–13
    [Google Scholar]
  211. 211. 
    Yokoyama N, Hayashi N, Seki T, Panté N, Ohba T et al. 1995. A giant nucleopore protein that binds Ran/TC4. Nature 376:184–88
    [Google Scholar]
  212. 212. 
    Lin DH, Zimmermann S, Stuwe T, Stuwe E, Hoelz A 2013. Structural and functional analysis of the C-terminal domain of Nup358/RanBP2. J. Mol. Biol. 425:1318–29
    [Google Scholar]
  213. 213. 
    Kassube SA, Stuwe T, Lin DH, Antonuk CD, Napetschnig J et al. 2012. Crystal structure of the N-terminal domain of Nup358/RanBP2. J. Mol. Biol. 423:752–65
    [Google Scholar]
  214. 214. 
    Vetter IR, Nowak C, Nishimoto T, Kuhlmann J, Wittinghofer A 1999. Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Nature 398:39–46
    [Google Scholar]
  215. 215. 
    Reverter D, Lima CD. 2005. Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complex. Nature 435:687–92
    [Google Scholar]
  216. 216. 
    Joseph J, Dasso M. 2008. The nucleoporin Nup358 associates with and regulates interphase microtubules. FEBS Lett 582:190–96
    [Google Scholar]
  217. 217. 
    Bernad R, van der Velde H, Fornerod M, Pickersgill H 2004. Nup358/RanBP2 attaches to the nuclear pore complex via association with Nup88 and Nup214/CAN and plays a supporting role in CRM1-mediated nuclear protein export. Mol. Cell. Biol. 24:2373–84
    [Google Scholar]
  218. 218. 
    Mahadevan K, Zhang H, Akef A, Cui XA, Gueroussov S et al. 2013. RanBP2/Nup358 potentiates the translation of a subset of mRNAs encoding secretory proteins. PLOS Biol 11:e1001545
    [Google Scholar]
  219. 219. 
    Hamada M, Haeger A, Jeganathan KB, van Ree JH, Malureanu L et al. 2011. Ran-dependent docking of importin-β to RanBP2/Nup358 filaments is essential for protein import and cell viability. J. Cell Biol. 194:597–612
    [Google Scholar]
  220. 220. 
    Hutten S, Walde S, Spillner C, Hauber J, Kehlenbach RH 2009. The nuclear pore component Nup358 promotes transportin-dependent nuclear import. J. Cell Sci. 122:1100–10
    [Google Scholar]
  221. 221. 
    Hutten S, Flotho A, Melchior F, Kehlenbach RH 2008. The Nup358-RanGAP complex is required for efficient importin α/β-dependent nuclear import. Mol. Biol. Cell 19:2300–10
    [Google Scholar]
  222. 222. 
    Ritterhoff T, Das H, Hofhaus G, Schroder RR, Flotho A, Melchior F 2016. The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes. Nat. Commun. 7:11482
    [Google Scholar]
  223. 223. 
    Köhler A, Hurt E. 2010. Gene regulation by nucleoporins and links to cancer. Mol. Cell 38:6–15
    [Google Scholar]
  224. 224. 
    Partridge JR, Schwartz TU. 2009. Crystallographic and biochemical analysis of the Ran-binding zinc finger domain. J. Mol. Biol. 391:375–89
    [Google Scholar]
  225. 225. 
    Hase ME, Kuznetsov NV, Cordes VC 2001. Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to the nuclear pore complex but not parallel, in-register homodimerization. Mol. Biol. Cell 12:2433–52
    [Google Scholar]
  226. 226. 
    Matsuura Y, Stewart M. 2005. Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling. EMBO J 24:3681–89
    [Google Scholar]
  227. 227. 
    Walther TC, Fornerod M, Pickersgill H, Goldberg M, Allen TD, Mattaj IW 2001. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins. EMBO J 20:5703–14
    [Google Scholar]
  228. 228. 
    Hase ME, Cordes VC. 2003. Direct interaction with Nup153 mediates binding of Tpr to the periphery of the nuclear pore complex. Mol. Biol. Cell 14:1923–40
    [Google Scholar]
  229. 229. 
    Galy V, Olivo-Marin JC, Scherthan H, Doye V, Rascalou N, Nehrbass U 2000. Nuclear pore complexes in the organization of silent telomeric chromatin. Nature 403:108–12
    [Google Scholar]
  230. 230. 
    Vasu S, Shah S, Orjalo A, Park M, Fischer WH, Forbes DJ 2001. Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J. Cell Biol. 155:339–54
    [Google Scholar]
  231. 231. 
    Niño CA, Guet D, Gay A, Brutus S, Jourquin F et al. 2016. Posttranslational marks control architectural and functional plasticity of the nuclear pore complex basket. J. Cell Biol. 212:167–80
    [Google Scholar]
  232. 232. 
    Krull S, Thyberg J, Björkroth B, Rackwitz HR, Cordes VC 2004. Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket. Mol. Biol. Cell 15:4261–77
    [Google Scholar]
  233. 233. 
    Bayliss R, Littlewood T, Strawn LA, Wente SR, Stewart M 2002. GLFG and FxFG nucleoporins bind to overlapping sites on importin-β. J. Biol. Chem. 277:50597–606
    [Google Scholar]
  234. 234. 
    Bayliss R, Littlewood T, Stewart M 2000. Structural basis for the interaction between FxFG nucleoporin repeats and importin-β in nuclear trafficking. Cell 102:99–108
    [Google Scholar]
  235. 235. 
    Koyama M, Hirano H, Shirai N, Matsuura Y 2017. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p. Genes Cells 22:861–75
    [Google Scholar]
  236. 236. 
    Koyama M, Shirai N, Matsuura Y 2014. Structural insights into how Yrb2p accelerates the assembly of the Xpo1p nuclear export complex. Cell Rep 9:983–95
    [Google Scholar]
  237. 237. 
    Port SA, Monecke T, Dickmanns A, Spillner C, Hofele R et al. 2015. Structural and functional characterization of CRM1-Nup214 interactions reveals multiple FG-binding sites involved in nuclear export. Cell Rep 13:690–702
    [Google Scholar]
  238. 238. 
    Milles S, Mercadante D, Aramburu IV, Jensen MR, Banterle N et al. 2015. Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell 163:734–45
    [Google Scholar]
  239. 239. 
    Hough LE, Dutta K, Sparks S, Temel DB, Kamal A et al. 2015. The molecular mechanism of nuclear transport revealed by atomic-scale measurements. eLife 4:e10027
    [Google Scholar]
  240. 240. 
    Liu SM, Stewart M. 2005. Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-β homologue, Kap95p. J. Mol. Biol. 349:515–25
    [Google Scholar]
  241. 241. 
    Bayliss R, Leung SW, Baker RP, Quimby BB, Corbett AH, Stewart M 2002. Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats. EMBO J 21:2843–53
    [Google Scholar]
  242. 242. 
    Bayliss R, Ribbeck K, Akin D, Kent HM, Feldherr CM et al. 1999. Interaction between NTF2 and xFxFG-containing nucleoporins is required to mediate nuclear import of RanGDP. J. Mol. Biol. 293:579–93
    [Google Scholar]
  243. 243. 
    Grant RP, Neuhaus D, Stewart M 2003. Structural basis for the interaction between the Tap/NXF1 UBA domain and FG nucleoporins at 1 Å resolution. J. Mol. Biol. 326:849–58
    [Google Scholar]
  244. 244. 
    Fribourg S, Braun IC, Izaurralde E, Conti E 2001. Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. Mol. Cell 8:645–56
    [Google Scholar]
  245. 245. 
    Kobayashi J, Matsuura Y. 2013. Structural basis for cell-cycle-dependent nuclear import mediated by the karyopherin Kap121p. J. Mol. Biol. 425:1852–68
    [Google Scholar]
  246. 246. 
    Kralt A, Jagalur NB, van den Boom V, Lokareddy RK, Steen A et al. 2015. Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins. Mol. Biol. Cell 26:3301–12
    [Google Scholar]
  247. 247. 
    Ibarra A, Hetzer MW. 2015. Nuclear pore proteins and the control of genome functions. Genes Dev 29:337–49
    [Google Scholar]
  248. 248. 
    Matsuura Y, Lange A, Harreman MT, Corbett AH, Stewart M 2003. Structural basis for Nup2p function in cargo release and karyopherin recycling in nuclear import. EMBO J 22:5358–69
    [Google Scholar]
  249. 249. 
    Yaseen NR, Blobel G. 1999. Two distinct classes of Ran-binding sites on the nucleoporin Nup-358. PNAS 96:5516–21
    [Google Scholar]
  250. 250. 
    Schrader N, Koerner C, Koessmeier K, Bangert JA, Wittinghofer A et al. 2008. The crystal structure of the Ran-Nup153ZnF2 complex: a general Ran docking site at the nuclear pore complex. Structure 16:1116–25
    [Google Scholar]
  251. 251. 
    Mahajan R, Delphin C, Guan T, Gerace L, Melchior F 1997. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88:97–107
    [Google Scholar]
  252. 252. 
    Werner A, Flotho A, Melchior F 2012. The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Mol. Cell 46:287–98
    [Google Scholar]
  253. 253. 
    Matunis MJ, Wu J, Blobel G 1998. SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J. Cell Biol. 140:499–509
    [Google Scholar]
  254. 254. 
    Rodríguez-Navarro S, Hurt E. 2011. Linking gene regulation to mRNA production and export. Curr. Opin. Cell Biol. 23:302–9
    [Google Scholar]
  255. 255. 
    Pascual-Garcia P, Capelson M. 2014. Nuclear pores as versatile platforms for gene regulation. Curr. Opin. Genet. Dev. 25:110–17
    [Google Scholar]
  256. 256. 
    Fischer T, Sträßer K, Rácz A, Rodríguez-Navarro S, Oppizzi M et al. 2002. The mRNA export machinery requires the novel Sac3p–Thp1p complex to dock at the nucleoplasmic entrance of the nuclear pores. EMBO J 21:5843–52
    [Google Scholar]
  257. 257. 
    Fischer T, Rodríguez-Navarro S, Pereira G, Rácz A, Schiebel E, Hurt E 2004. Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery. Nat. Cell Biol. 6:840–48
    [Google Scholar]
  258. 258. 
    Jani D, Valkov E, Stewart M 2014. Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export. Nucleic Acids Res 42:6686–97
    [Google Scholar]
  259. 259. 
    Jani D, Lutz S, Hurt E, Laskey RA, Stewart M, Wickramasinghe VO 2012. Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export. Nucleic Acids Res 40:4562–73
    [Google Scholar]
  260. 260. 
    Umlauf D, Bonnet J, Waharte F, Fournier M, Stierle M et al. 2013. The human TREX-2 complex is stably associated with the nuclear pore basket. J. Cell Sci. 126:2656–67
    [Google Scholar]
  261. 261. 
    Xu S, Powers MA. 2009. Nuclear pore proteins and cancer. Semin. Cell Dev. Biol. 20:620–30
    [Google Scholar]
  262. 262. 
    Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S et al. 2015. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525:129–33
    [Google Scholar]
  263. 263. 
    Joviĉić A, Mertens J, Boeynaems S, Bogaert E, Chai N et al. 2015. Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS. Nat. Neurosci. 18:1226–29
    [Google Scholar]
  264. 264. 
    Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB et al. 2015. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525:56–61
    [Google Scholar]
  265. 265. 
    Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K et al. 2017. Mutant Huntingtin disrupts the nuclear pore complex. Neuron 94:93–107.e6
    [Google Scholar]
  266. 266. 
    Toyama BH, Savas JN, Park SK, Harris MS, Ingolia NT et al. 2013. Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell 154:971–82
    [Google Scholar]
  267. 267. 
    Tullio-Pelet A, Salomon R, Hadj-Rabia S, Mugnier C, de Laet MH et al. 2000. Mutant WD-repeat protein in triple-A syndrome. Nat. Genet. 26:332–35
    [Google Scholar]
  268. 268. 
    Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A 2001. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum. Mol. Genet. 10:283–90
    [Google Scholar]
  269. 269. 
    Basel-Vanagaite L, Muncher L, Straussberg R, Pasmanik-Chor M, Yahav M et al. 2006. Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis. Ann. Neurol. 60:214–22
    [Google Scholar]
  270. 270. 
    Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM et al. 2009. Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore. RANBP2. Am. J. Hum. Genet. 84:44–51
    [Google Scholar]
  271. 271. 
    Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsunaga S et al. 2015. Biallelic mutations in nuclear pore complex subunit NUP107 cause early-childhood-onset steroid-resistant nephrotic syndrome. Am. J. Hum. Genet. 97:555–66
    [Google Scholar]
  272. 272. 
    Kaneb HM, Folkmann AW, Belzil VV, Jao LE, Leblond CS et al. 2015. Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. Hum. Mol. Genet. 24:1363–73
    [Google Scholar]
  273. 273. 
    Zhang X, Chen S, Yoo S, Chakrabarti S, Zhang T et al. 2008. Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell 135:1017–27
    [Google Scholar]
  274. 274. 
    Folkmann AW, Dawson TR, Wente SR 2014. Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure–function analysis. Adv. Biol. Regul. 54:74–91
    [Google Scholar]
  275. 275. 
    Park E, Ahn YH, Kang HG, Miyake N, Tsukaguchi H, Cheong HI 2017. NUP107 mutations in children with steroid-resistant nephrotic syndrome. Nephrol. Dial. Transplant. 32:1013–17
    [Google Scholar]
  276. 276. 
    Braun DA, Sadowski CE, Kohl S, Lovric S, Astrinidis SA et al. 2016. Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nat. Genet. 48:457–65
    [Google Scholar]
  277. 277. 
    Park M, Dean M, Cooper CS, Schmidt M, O'Brien SJ et al. 1986. Mechanism of met oncogene activation. Cell 45:895–904
    [Google Scholar]
  278. 278. 
    Pal K, Bandyopadhyay A, Zhou XE, Xu Q, Marciano DP et al. 2017. Structural basis of TPR-mediated oligomerization and activation of oncogenic fusion kinases. Structure 25:867–77.e3
    [Google Scholar]
  279. 279. 
    Singer S, Zhao R, Barsotti AM, Ouwehand A, Fazollahi M et al. 2012. Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Mol. Cell 48:799–810
    [Google Scholar]
  280. 280. 
    Cohen S, Au S, Panté N 2011. How viruses access the nucleus. Biochim. Biophys. Acta Mol. Cell Res. 1813:1634–45
    [Google Scholar]
  281. 281. 
    Le Sage V, Mouland AJ 2013. Viral subversion of the nuclear pore complex. Viruses 5:2019–42
    [Google Scholar]
  282. 282. 
    Yarbrough ML, Mata MA, Sakthivel R, Fontoura BM 2014. Viral subversion of nucleocytoplasmic trafficking. Traffic 15:127–40
    [Google Scholar]
  283. 283. 
    von Kobbe C, van Deursen JM, Rodrigues JP, Sitterlin D, Bachi A et al. 2000. Vesicular stomatitis virus matrix protein inhibits host cell gene expression by targeting the nucleoporin Nup98. Mol. Cell 6:1243–52
    [Google Scholar]
  284. 284. 
    Faria PA, Chakraborty P, Levay A, Barber GN, Ezelle HJ et al. 2005. VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway. Mol. Cell 17:93–102
    [Google Scholar]
  285. 285. 
    Di Nunzio F, Danckaert A, Fricke T, Perez P, Fernandez J et al. 2012. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration. PLOS ONE 7:e46037
    [Google Scholar]
  286. 286. 
    Arhel NJ, Souquere-Besse S, Munier S, Souque P, Guadagnini S et al. 2007. HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore. EMBO J 26:3025–37
    [Google Scholar]
  287. 287. 
    Schaller T, Ocwieja KE, Rasaiyaah J, Price AJ, Brady TL et al. 2011. HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLOS Pathog 7:e1002439
    [Google Scholar]
  288. 288. 
    Bichel K, Price AJ, Schaller T, Towers GJ, Freund SM, James LC 2013. HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358. Retrovirology 10:81
    [Google Scholar]
  289. 289. 
    Matreyek KA, Yücel SS, Li X, Engelman A 2013. Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity. PLOS Pathog 9:e1003693
    [Google Scholar]
  290. 290. 
    Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S et al. 2014. Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly. PLOS Pathog 10:e1004459
    [Google Scholar]
  291. 291. 
    Schmitz A, Schwarz A, Foss M, Zhou L, Rabe B et al. 2010. Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket. PLOS Pathog 6:e1000741
    [Google Scholar]
  292. 292. 
    Bono F, Cook AG, Grünwald M, Ebert J, Conti E 2010. Nuclear import mechanism of the EJC component Mago-Y14 revealed by structural studies of importin 13. Mol. Cell 37:211–22
    [Google Scholar]
  293. 293. 
    Monecke T, Güttler T, Neumann P, Dickmanns A, Görlich D, Ficner R 2009. Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP. Science 324:1087–91
    [Google Scholar]
  294. 294. 
    Murata K, Mitsuoka K, Hirai T, Walz T, Agre P et al. 2000. Structural determinants of water permeation through aquaporin-1. Nature 407:599–605
    [Google Scholar]
  295. 295. 
    van den Berg B, Black PN, Clemons WM Jr, Rapoport TA 2004. Crystal structure of the long-chain fatty acid transporter FadL. Science 304:1506–9
    [Google Scholar]
  296. 296. 
    Wu S, Tutuncuoglu B, Yan K, Brown H, Zhang Y et al. 2016. Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature 534:133–37
    [Google Scholar]
  297. 297. 
    Pumroy RA, Nardozzi JD, Hart DJ, Root MJ, Cingolani G 2012. Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin α5. J. Biol. Chem. 287:2022–31
    [Google Scholar]
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