Accurate folding, assembly, localization, and maturation of newly synthesized proteins are essential to all cells and require high fidelity in the protein biogenesis machineries that mediate these processes. Here, we review our current understanding of how high fidelity is achieved in one of these processes, the cotranslational targeting of nascent membrane and secretory proteins by the signal recognition particle (SRP). Recent biochemical, biophysical, and structural studies have elucidated how the correct substrates drive a series of elaborate conformational rearrangements in the SRP and SRP receptor GTPases; these rearrangements provide effective fidelity checkpoints to reject incorrect substrates and enhance the fidelity of this essential cellular pathway. The mechanisms used by SRP to ensure fidelity share important conceptual analogies with those used by cellular machineries involved in DNA replication, transcription, and translation, and these mechanisms likely represent general principles for other complex cellular pathways.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Akopian D, Dalai K, Shen K, Duong F, Shan S. 1.  2013. SecYEG activates GTPases to drive the completion of cotranslational protein targeting. J. Cell Biol. 200:397–405 [Google Scholar]
  2. Akopian D, Shen K, Zhang X, Shan S. 2.  2013. Signal recognition particle: an essential protein-targeting machine. Annu. Rev. Biochem. 82:693–721 [Google Scholar]
  3. Albanèse V, Yam AY-W, Baughman J, Parnot C, Frydman J. 3.  2006. Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124:75–88 [Google Scholar]
  4. Ataide SF, Schmitz N, Shen K, Ke A, Shan S. 4.  et al. 2011. The crystal structure of the signal recognition particle in complex with its receptor. Science 381:881–86 [Google Scholar]
  5. Bange G, Kummerer N, Grudnik P, Lindner R, Petzold G. 5.  et al. 2011. Structural basis for the molecular evolution of SRP-GTPase activation by protein. Nat. Struct. Mol. Biol. 18:1376–80 [Google Scholar]
  6. Batey RT, Rambo RP, Lucast L, Rha B, Doudna JA. 6.  2000. Crystal structure of the ribonucleoprotein core of the signal recognition particle. Science 287:1232–39 [Google Scholar]
  7. Batey RT, Sagar MB, Doudna JA. 7.  2001. Structural and energetic analysis of RNA recognition by a universally conserved protein from the signal recognition particle. J. Mol. Biol. 307:229–46 [Google Scholar]
  8. Beck K, Wu L-F, Brunner J, Müller M. 8.  2000. Discrimination between SRP- and SecA/SecB-dependent substrates involves selective recognition of nascent chains by SRP and trigger factor. EMBO J. 19:134–43 [Google Scholar]
  9. Becker T, Bhushan S, Jarasch A, Armache J-P, Funes S. 9.  et al. 2009. Structure of monomeric yeast and mammalian Sec61 complexes interacting with the translating ribosome. Science 326:1367–73 [Google Scholar]
  10. Beckmann R, Spahn CMT, Eswar N, Helmers J, Penczek PA. 10.  et al. 2001. Architecture of the protein-conducting channel associated with the translating 80S ribosome. Cell 107:361–72 [Google Scholar]
  11. Berndt U, Oellerer S, Zhang Y, Johnson AE, Rospert S. 11.  2009. A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel. Proc. Natl. Acad. Sci. USA 106:1398–403 [Google Scholar]
  12. Bernstein HD, Poritz MA, Strub K, Hoben PJ, Brenner S, Walter P. 12.  1989. Model for signal sequence recognition from amino-acid sequence of 54K subunit of signal recognition particle. Nature 340:482–86 [Google Scholar]
  13. Bernstein HD, Zopf D, Freymann DM, Walter P. 13.  1993. Functional substitution of the signal recognition particle 54-kDa subunit by its Escherichia coli homolog. Proc. Natl. Acad. Sci. USA 90:5229–34 [Google Scholar]
  14. Blobel G, Sabatini DD. 14.  1971. Ribosome–membrane interaction in eukaryotic cells. Biomembranes LA Manson 193–95 New York: Plenum [Google Scholar]
  15. Bornemann T, Jockel J, Rodnina MV, Wintermeyer W. 15.  2008. Signal sequence–independent membrane targeting of ribosomes containing short nascent peptides within the exit tunnel. Nat. Struct. Mol. Biol. 15:494–99 [Google Scholar]
  16. Bourne HR, Sanders DA, McCormick F. 16.  1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–28 [Google Scholar]
  17. Bradshaw N, Neher SB, Booth DS, Walter P. 17.  2009. Signal sequences activate the catalytic switch of SRP RNA. Science 323:127–30 [Google Scholar]
  18. Brandman O, Stewart-Omstein J, Wong D, Larson A, Williams CC. 18.  et al. 2012. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell 151:1042–54 [Google Scholar]
  19. Buskiewicz I, Deuerling E, Gu SQ, Jockel J, Rodnina MV. 19.  et al. 2004. Trigger factor binds to ribosome-signal-recognition particle (SRP) complexes and is excluded by binding of the SRP receptor. Proc. Natl. Acad. Sci. USA 101:7902–06 [Google Scholar]
  20. Buskiewicz I, Jockel J, Rodnina MV, Wintermeyer W. 20.  2009. Conformation of the signal recognition particle in ribosomal targeting complexes. RNA 15:44–54 [Google Scholar]
  21. Buskiewicz I, Kubarenko A, Peske F, Rodnina MV, Wintermeyer W. 21.  2005. Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY. RNA 11:947–57 [Google Scholar]
  22. Buskiewicz I, Peske F, Wieden H-J, Gryczynski I, Rodnina MV, Wintermeyer W. 22.  2005. Conformations of the signal recognition particle protein Ffh from Escherichia coli as determined by FRET. J. Mol. Biol. 351:417–30 [Google Scholar]
  23. Chappie JS, Acharya S, Leonard M, Schmid SL, Dyda F. 23.  2010. G domain dimerization controls dynamin's assembly-stimulated GTPase activity. Nature 465:435–40 [Google Scholar]
  24. Connolly T, Rapiejko PJ, Gilmore R. 24.  1991. Requirement of GTP hydrolysis for dissociation of the signal recognition particle from its receptor. Science 252:1171–73 [Google Scholar]
  25. Cross BCS, Sinning I, Luirink J, High S. 25.  2009. Delivering proteins for export from the cytosol. Nat. Rev. Mol. Cell Biol. 10:255–64 [Google Scholar]
  26. Cruz-Vera LR, Gong M, Yanofsky C. 26.  2006. Changes produced by bound tryptophan in the ribosome peptidyl transferase center in response to TnaC, a nascent leader peptide. Proc. Natl. Acad. Sci. USA 103:3598–603 [Google Scholar]
  27. Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R. 27.  1988. A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332:800–5 [Google Scholar]
  28. del Alamo M, Hogan DJ, Pechmann S, Albanese V, Brown PO, Frydman J. 28.  2011. Defining the specificity of cotranslationally acting chaperones by systematic analysis of mRNAs associated with ribosome-nascent chain complexes. PLoS Biol. 9:e1001100 [Google Scholar]
  29. Deuerling E, Schulze-Specking A, Tomoyasu T, Mogk A, Bukau B. 29.  1999. Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400:693–96 [Google Scholar]
  30. Driessen AJM, Nouwen N. 30.  2008. Protein translocation across the bacterial cytoplasmic membrane. Annu. Rev. Biochem. 77:643–67 [Google Scholar]
  31. Dudek J, Rehling P, van der Laan M. 31.  2013. Mitochondrial protein import: common principles and physiological networks. Biochim. Biophys. Acta 1833:274–85 [Google Scholar]
  32. Egea PF, Shan S, Napetschnig J, Savage DF, Walter P, Stroud RM. 32.  2004. Substrate twinning activates the signal recognition particle and its receptor. Nature 427:215–21 [Google Scholar]
  33. Eisner G, Moser M, Schäfer U, Beck K, Müller M. 33.  2006. Alternative recruitment of signal recognition particle and trigger factor to the signal sequence of a growing nascent polypeptide. J. Biol. Chem. 281:7172–79 [Google Scholar]
  34. Emanuelsson O, Nielson H, von Heijne G. 34.  1999. ChloroP, a neural network-based method for predicting chloroplast transit peptides and their cleavage sites. Protein Sci. 8:978–84 [Google Scholar]
  35. Estrozi LF, Boehringer D, Shan S, Ban N, Schaffitzel C. 35.  2011. Cryo-EM structure of the E. coli translating ribosome in complex with SRP and its receptor. Nat. Struct. Mol. Biol. 18:88–90 [Google Scholar]
  36. Fersht A. 36.  1984. Enzyme Structure and Mechanism New York: Freeman
  37. Fersht AR, Dingwall C. 37.  1979. Evidence for the double-sieve editing mechanism in protein synthesis. Steric exclusion of isoleucine by valyl-tRNA synthetases. Biochemistry 18:2627–31 [Google Scholar]
  38. Fersht AR, Kaethner MM. 38.  1976. Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing. Biochemistry 15:3342–46 [Google Scholar]
  39. Flanagan JJ, Chen J-C, Miao Y, Shao Y, Lin J. 39.  et al. 2003. Signal recognition particle binds to ribosome-bound signal sequences with fluorescence-detected subnanomolar affinity that does not diminish as the nascent chain lengthens. J. Biol. Chem. 278:18628–37 [Google Scholar]
  40. Focia PJ, Shepotinovskaya IV, Seidler JA, Freymann DM. 40.  2004. Heterodimeric GTPase core of the SRP targeting complex. Science 303:373–77 [Google Scholar]
  41. Fraunfeld J, Gumbart J, Sluis EO, Funes S, Gartmann M. 41.  et al. 2011. Cryo-EM structure of the ribosome–SecYE complex in the membrane environment. Nat. Struct. Mol. Biol. 18:614–21 [Google Scholar]
  42. Freymann DM, Walter P. 42.  2000. GTPases in protein translocation and protein elongation. Frontiers in Molecular Biology: GTPases A Hall 222–43 London: Oxford Univ. Press [Google Scholar]
  43. Freymann DM, Keenan RJ, Stroud RM, Walter P. 43.  1997. Structure of the conserved GTPase domain of the signal recognition particle. Nature 385:361–64 [Google Scholar]
  44. Freymann DM, Keenan RJ, Stroud RM, Walter P. 44.  1999. Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP. Nat. Struct. Biol. 6:793–801 [Google Scholar]
  45. Fröbel J, Rose P, Müller M. 45.  2012. Twin-arginine-dependent translocation of folded proteins. Philos. Trans. R. Soc. Lond. B. 367:1029–46 [Google Scholar]
  46. Gasper R, Meyer S, Gotthardt K, Sirajuddin M, Wittinghofer A. 46.  2009. It takes two to tango: regulation of G proteins by dimerization. Nat. Rev. Mol. Cell Biol. 10:423–29 [Google Scholar]
  47. Gawronski-Salerno J, Coon YJS, Focia PJ, Freymann DM. 47.  2006. X-ray structure of the T. Aquaticus Ftsy:GDP complex suggests functional roles for the C-terminal helix of the SRP GTPases. Proteins 66:984–95 [Google Scholar]
  48. Gawronski-Salerno J, Freymann DM. 48.  2007. Structure of the GMPPNP-stabilized NG domain complex of the SRP GTPases Ffh and FtsY. J. Struct. Biol. 158:122–28 [Google Scholar]
  49. Gierasch LM. 49.  1989. Signal sequences. Biochemistry 28:923–30 [Google Scholar]
  50. Gilman AG. 50.  1987. G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56:615–49 [Google Scholar]
  51. Goldshmidt H, Sheiner L, Bütikofer P, Roditi I, Uliel S. 51.  et al. 2008. Role of protein translocation pathways across the endoplasmic reticulum in Trypanosoma brucei. J. Biol. Chem. 283:32085–98 [Google Scholar]
  52. Gu SQ, Peske F, Wieden HJ, Rodnina MV, Wintermeyer W. 52.  2003. The signal recognition particle binds to protein L23 at the peptide exit of the Escherichia coli ribosome. RNA 9:566–73 [Google Scholar]
  53. Hainzl T, Huang S, Sauer-Eriksson AE. 53.  2007. Interaction of signal-recognition particle 54 GTPase domain and signal-recognition particle RNA in the free signal-recognition particle. Proc. Natl. Acad. Sci. USA 104:14911–16 [Google Scholar]
  54. Hainzl T, Huang S, Meriläinen G, Brännström K, Sauer-Eriksson AE. 54.  2011. Structural basis of signal-sequence recognition by the signal recognition particle. Nat. Struct. Mol. Biol. 18:389–91 [Google Scholar]
  55. Halic M, Becker T, Pool MR, Spahn CMT, Grassucci RA. 55.  et al. 2004. Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427:808–14 [Google Scholar]
  56. Halic M, Blau M, Becker T, Mielke T, Pool MR. 56.  et al. 2006. Following the signal sequence from ribosomal tunnel exit to signal recognition particle. Nature 444:507–11 [Google Scholar]
  57. Halic M, Gartmann M, Schlenker O, Mielke T, Pool MR. 57.  et al. 2006. Signal recognition particle receptor exposes the ribosomal translocon binding site. Science 312:745–47 [Google Scholar]
  58. Hartl FU, Bracher A, Hayer-Hartl M. 58.  2011. Molecular chaperones in protein folding and proteostasis. Nature 475:324–32 [Google Scholar]
  59. Hegde RS, Keenan RJ. 59.  2011. Tail-anchored membrane protein insertion into the endoplasmic reticulum. Nat. Rev. Mol. Cell Biol. 12:787–98 [Google Scholar]
  60. Hodel MR, Corbett AH, Hodel AE. 60.  2001. Dissection of a nuclear localization signal. J. Biol. Chem. 276:1317–25 [Google Scholar]
  61. Hoffmann A, Becker AH, Zachmann-Brand B, Deuerling E, Bukau B, Kramer G. 61.  2012. Concerted action of the ribosome and the associated chaperone Trigger Factor confines nascent polypeptide folding. Mol. Cell 48:63–74 [Google Scholar]
  62. Holtkamp W, Lee S, Bornemann T, Senyushkina T, Rodnina MV, Wintermeyer W. 62.  2012. Dynamic switch of the signal recognition particle from scanning to targeting. Nat. Struct. Mol. Biol. 19:1332–37 [Google Scholar]
  63. Huang P, Gautschi M, Walter W, Rospert S, Craig EA. 63.  2005. The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1. Nat. Struct. Mol. Biol. 12:497–504 [Google Scholar]
  64. Huber D, Boyd D, Xia Y, Olma MH, Gerstein M, Beckwith J. 64.  2005. Use of thioredoxin as a reporter to identify a subset of Escherichia coli signal sequences that promote signal recognition particle–dependent translocation. J. Bacteriol. 187:2983–91 [Google Scholar]
  65. Ito-Harashima S, Kuroha K, Tatematsu T, Inada T. 65.  2007. Translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization by proteasome in yeast. Genes Dev. 21:519–24 [Google Scholar]
  66. Janda CY, Li J, Oubridge C, Hernandez H, Robinson CV, Nagai K. 66.  2010. Recognition of a signal peptide by the signal recognition particle. Nature 465:507–10 [Google Scholar]
  67. Johnson AE, van Waes MA. 67.  1999. The translocon: A dynamic gateway at the ER membrane. Annu. Rev. Cell Dev. Biol. 18:799–842 [Google Scholar]
  68. Jones JD, McKnight CJ, Gierasch LM. 68.  1990. Biophysical studies of signal peptides: implications for signal sequence functions and the involvement of lipid in protein export. J. Bioenerg. Biomembr. 22:213–32 [Google Scholar]
  69. Jungnickel B, Rapoport TA. 69.  1995. A posttargeting signal sequence recognition event in the endoplasmic reticulum membrane. Cell 82:261–70 [Google Scholar]
  70. Kaiser CM, Chang H-C, Agashe VR, Lakshmipathy SK, Etchells SA. 70.  et al. 2006. Real-time observation of trigger factor function on translating ribosomes. Nature 444:455–60 [Google Scholar]
  71. Keenan RJ, Freymann DM, Stroud RM, Walter P. 71.  2001. The signal recognition particle. Annu. Rev. Biochem. 70:755–75 [Google Scholar]
  72. Keenan RJ, Freymann DM, Walter P, Stroud RM. 72.  1998. Crystal structure of the signal sequence binding subunit of the signal recognition particle. Cell 94:181–91 [Google Scholar]
  73. Knoops K, Schoehn G, Schaffitzel C. 73.  2011. Cryo-electron microscopy of ribosomal complexes in cotranslational folding, targeting, and translocation. WIREs RNA 3:429–41 [Google Scholar]
  74. Kramer G, Boehringer D, Ban N, Bukau B. 74.  2009. The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat. Struct. Mol. Biol. 16:589–97 [Google Scholar]
  75. Kunkel TA, Bebenek K. 75.  2000. DNA replication fidelity. Annu. Rev. Biochem. 69:497–529 [Google Scholar]
  76. Lakkaraju AKK, Mary C, Scherrer A, Johnson AE, Strub K. 76.  2008. SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites. Cell 133:440–51 [Google Scholar]
  77. Lam VQ, Akopian D, Rome M, Shen Y, Henningsen D, Shan S. 77.  2010. Lipid activation of the SRP receptor provides spatial coordination of protein targeting. J. Cell Biol. 190:623–35 [Google Scholar]
  78. Lee DW, Jung C, Hwang I. 78.  2013. Cytosolic events involved in chloroplast protein targeting. Biochim. Biophys. Acta 1833:245–52 [Google Scholar]
  79. Lee HC, Bernstein HD. 79.  2002. Trigger factor retards protein export in Escherichia coli. J. Biol. Chem. 277:43527–35 [Google Scholar]
  80. Leipe DD, Wolf YI, Koonin EV, Aravid L. 80.  2002. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317:41–72 [Google Scholar]
  81. Liao S, Lin J, Do H, Johnson AE. 81.  1997. Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90:31–41 [Google Scholar]
  82. Lu J, Deutsch C. 82.  2005. Folding zones inside the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 12:1123–29 [Google Scholar]
  83. Mainprize IL, Beniac DR, Falkovskaia E, Cleverley RM, Gierasch LM. 83.  et al. 2006. The structure of Escherichia coli signal recognition particle revealed by scanning transmission electron microscopy. Mol. Biol. Cell 17:5063–74 [Google Scholar]
  84. Mariappan M, Li X, Stefanovic S, Sharma A, Mateja A. 84.  et al. 2010. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature 466:1120–24 [Google Scholar]
  85. McClellan AJ, Xia Y. 85.  2007. Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches. Cell 131:121–35 [Google Scholar]
  86. Melville MW, McClellan AJ, Meyer AS, Darvaeu A, Frydman J. 86.  2003. The Hsp70 and TriC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Mol. Cell. Biol. 23:3141–51 [Google Scholar]
  87. Merz F, Boehringer D, Schaffitzel C, Preissler S, Hoffmann A. 87.  et al. 2008. Molecular mechanism and structure of Trigger Factor bound to the translating ribosome. EMBO J. 27:1622–32 [Google Scholar]
  88. Mitra K, Schaffitzel C, Shaikh T, Tama F, Jenni S. 88.  et al. 2005. Structure of the E. coli protein-conducting channel bound to a translating ribosome. Nature 438:318–24 [Google Scholar]
  89. Montoya G, Svensson C, Luirink J, Sinning I. 89.  1997. Crystal structure of the NG domain from the signal recognition particle receptor FtsY. Nature 385:365–68 [Google Scholar]
  90. Nakatogawa HA, Ito K. 90.  2001. Secretion motor, SecM, undergoes self-translation arrest in the cytosol. Mol. Cell 7:185–92 [Google Scholar]
  91. Natale P, Brüser T, Driessen AJM. 91.  2008. Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane—distinct translocases and mechanisms. Biochim. Biophys. Acta 1778:1735–56 [Google Scholar]
  92. Neher SB, Bradshaw N, Floor SN, Gross JD, Walter P. 92.  2008. SRP RNA controls a conformational switch regulating the SRP–SRP receptor interaction. Nat. Struct. Mol. Biol. 15:916–23 [Google Scholar]
  93. Netzer WJ, Hartl FU. 93.  1998. Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms. Trends Biochem. Sci. 23:68–73 [Google Scholar]
  94. Ogg SC, Walter P. 94.  1995. SRP samples nascent chains for the presence of signal sequences by interacting with ribosomes at a discrete step during translation elongation. Cell 81:1075–84 [Google Scholar]
  95. Ogle JM, Ramakrishnan V. 95.  2005. Structural insights into translational fidelity. Annu. Rev. Biochem. 74:129–77 [Google Scholar]
  96. Oh E, Becker AH, Sandikci A, Huber D, Chaba R. 96.  et al. 2011. Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo. Cell 147:1295–308 [Google Scholar]
  97. Padmanabhan W, Freymann DM. 97.  2001. The conformation of bound GMPPNP suggests a mechanism for gating the active site of the SRP GTPase. Structure 9:859–63 [Google Scholar]
  98. Parlitz R, Eitan A, Stjepanovic G, Bahari L, Bange G. 98.  et al. 2007. Escherichia coli signal recognition particle receptor FtsY contains an essential and autonomous membrane-binding amphipathic helix. J. Biol. Chem. 282:32176–84 [Google Scholar]
  99. Pechmann S, Willmund F, Frydman J. 99.  2013. The ribosome as a hub for protein quality control. Mol. Cell 49:411–21 [Google Scholar]
  100. Peluso P, Herschlag D, Nock S, Freymann DM, Johnson AE, Walter P. 100.  2000. Role of 4.5S RNA in assembly of the bacterial signal recognition particle with its receptor. Science 288:1640–43 [Google Scholar]
  101. Peluso P, Shan S, Nock S, Herschlag D, Walter P. 101.  2001. Role of SRP RNA in the GTPase cycles of Ffh and FtsY. Biochemistry 40:15224–33 [Google Scholar]
  102. Peterson JH, Szabady RL, Bernstein HD. 102.  2006. An unusual signal peptide extension inhibits the binding of bacterial presecretory proteins to the signal recognition particle, trigger factor, and the secYEG complex. J. Biol. Chem. 281:9038–48 [Google Scholar]
  103. Pool MR. 103.  2009. A trans-membrane segment inside the ribosome exit tunnel triggers RAMP4 recruitment to the Sec61p translocase. J. Cell Biol. 185:889–902 [Google Scholar]
  104. Pool MR, Stumm J, Fulga TA, Sinning I, Dobberstein B. 104.  2002. Distinct modes of signal recognition particle interaction with the ribosome. Science 297:1345–48 [Google Scholar]
  105. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. 105.  2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959–91 [Google Scholar]
  106. Powers T, Walter P. 106.  1995. Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases. Science 269:1422–24 [Google Scholar]
  107. Powers T, Walter P. 107.  1996. The nascent polypeptide-associated complex modulates interactions between the signal recognition particle and the ribosome. Curr. Biol. 6:331–38 [Google Scholar]
  108. Powers T, Walter P. 108.  1997. Co-translational protein targeting catalyzed by the Escherichia coli signal recognition particle and its receptor. EMBO J. 16:4880–86 [Google Scholar]
  109. Randall LL, Hardy SJS. 109.  1995. High selectivity with low specificity: how SecB has solved the paradox of chaperone binding. Trends Biochem. Sci. 20:65–69 [Google Scholar]
  110. Rapoport TA. 110.  2007. Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450:663–69 [Google Scholar]
  111. Rapoport TA, Heinrich R, Walter P, Schulmeister T. 111.  1987. Mathematical modeling of the effects of the signal recognition particle on translation and translocation of proteins across the endoplasmic reticulum membrane. J. Mol. Biol. 195:621–36 [Google Scholar]
  112. Rapoport TA, Jungnickel B, Kutay U. 112.  1996. Protein transport across the eukaryotic endoplasmic reticulum and bacterial inner membranes. Annu. Rev. Biochem. 65:271–303 [Google Scholar]
  113. Reyes CL, Rutenber E, Walter P, Stroud RM. 113.  2007. X-ray structures of the signal recognition particle receptor reveal targeting cycle intermediates. PLoS ONE 2:e607 [Google Scholar]
  114. Rodnina MV, Wintermeyer W. 114.  2001. Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms. Annu. Rev. Biochem. 70:415–35 [Google Scholar]
  115. Rodnina MV, Wintermeyer W. 115.  2001. Ribosome fidelity: tRNA discrimination, proofreading and induced fit. Trends Biochem. Sci. 26:124–30 [Google Scholar]
  116. Rosendal KR, Wild K, Montoya G, Sinning I. 116.  2003. Crystal structure of the complete core of archaeal signal recognition particle and implications for interdomain communication. Proc. Natl. Acad. Sci. USA 100:14701–06 [Google Scholar]
  117. Saibil HR, Fenton WA, Clare DK, Horwich AL. 117.  2013. Structure and allostery of the chaperonin GroEL. J. Mol. Biol. 425:1476–87 [Google Scholar]
  118. Saraogi I, Zhang D, Chandrasekaran S, Shan S. 118.  2011. Site-specific fluorescent labeling of nascent proteins on the translating ribosome. J. Am. Chem. Soc. 133:14936–39 [Google Scholar]
  119. Schaffitzel C, Oswald M, Berger I, Ishikawa T, Abrahams JP. 119.  et al. 2006. Structure of the E. coli signal recognition particle bound to a translating ribosome. Nature 444:503–06 [Google Scholar]
  120. Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M. 120.  et al. 2008. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell 134:634–45 [Google Scholar]
  121. Semlow DR, Staley JP. 121.  2012. Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem. Sci. 37:263–73 [Google Scholar]
  122. Shan S, Walter P. 122.  2003. Induced nucleotide specificity in a GTPase. Proc. Natl. Acad. Sci. USA 100:4480–85 [Google Scholar]
  123. Shan S, Chandrasekar S, Walter P. 123.  2007. Conformational changes in the GTPase modules of the signal reception particle and its receptor drive initiation of protein translocation. J. Cell Biol. 178:611–20 [Google Scholar]
  124. Shan S, Stroud R, Walter P. 124.  2004. Mechanism of association and reciprocal activation of two GTPases. PLoS Biol. 2:e320 [Google Scholar]
  125. Shen K, Shan S. 125.  2010. A transient tether between the SRP RNA and SRP receptor ensures efficient cargo delivery during cotranslational protein targeting. Proc. Natl. Acad. Sci. USA 107:7698–703 [Google Scholar]
  126. Shen K, Arslan S, Akopian D, Ha T, Shan S. 126.  2012. Activated GTPase movement on an RNA scaffold drives cotranslational protein targeting. Nature 492:271–75 [Google Scholar]
  127. Shen K, Zhang X, Shan S. 127.  2011. Synergistic actions between the SRP RNA and translating ribosome allows efficient delivery of correct cargos during cotranslational protein targeting. RNA 17:892–902 [Google Scholar]
  128. Shepotinovskaya IV, Freymann DM. 128.  2001. Conformational change of the N-domain on formation of the complex between the GTPase domains of Thermus aquaticus Ffh and FtsY. Biochem. Biophys. Acta 1597:107–14 [Google Scholar]
  129. Siegel V, Walter P. 129.  1988. Each of the activities of signal recognition particle (SRP) is contained within a distinct domain: analysis of biochemical mutants of SRP. Cell 52:39–49 [Google Scholar]
  130. Siegel V, Walter P. 130.  1988. The affinity of signal recognition particle for presecretory proteins is dependent on nascent chain length. EMBO J. 7:1769–75 [Google Scholar]
  131. Spanggord RJ, Siu F, Ke A, Doudna JA. 131.  2005. RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particle. Nat. Struct. Mol. Biol. 12:1116–22 [Google Scholar]
  132. Sydow JF, Cramer P. 132.  2009. RNA polymerase fidelity and transcriptional proofreading. Curr. Opin. Struct. Biol. 19:732–39 [Google Scholar]
  133. Taipale M, Krykbaeva I, Koeva M, Kayatekin C, Westover KD. 133.  et al. 2012. Quantitative analysis of Hsp90-client interactions reveals principles of substrate recognition. Cell 150:987–1001 [Google Scholar]
  134. Tasaki T, Sriram SM, Park KS, Kwon YT. 134.  2012. The N-end rule pathway. Annu. Rev. Biochem. 81:261–89 [Google Scholar]
  135. Ullers RS, Houben ENG, Raine A, ten Hagen-Jongman CM, Ehrenberg M. 135.  et al. 2003. Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome. J. Cell Biol. 161:679–84 [Google Scholar]
  136. Valent QA, Kendall DA, High S, Kusters R, Oudega B, Luirink J. 136.  1995. Early events in preprotein recognition in E. coli: interaction of SRP and trigger factor with nascent polypeptides. EMBO J. 14:5494–505 [Google Scholar]
  137. Verma R, Oania RS, Kolawa NJ, Deshaies RJ. 137.  2013. Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome. eLIFE 3:e00308 [Google Scholar]
  138. von Heijne G. 138.  1985. Signal sequences: the limits of variation. J. Mol. Biol. 184:99–105 [Google Scholar]
  139. von Loeffelholz O, Knoops K, Ariosa A, Zhang X, Karuppasamy M. 139.  et al. 2013. Structural basis of signal sequence surveillance and selection by the SRP–FtsY complex. Nat. Struct. Mol. Biol. 20:604–10 [Google Scholar]
  140. Walter P, Blobel G. 140.  1982. Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum. Nature 299:691–98 [Google Scholar]
  141. Walter P, Blobel G. 141.  1983. Disassembly and reconstitution of signal recognition particle. Cell 34:525–33 [Google Scholar]
  142. Walter P, Johnson AE. 142.  1994. Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane. Annu. Rev. Cell Biol. 10:87–119 [Google Scholar]
  143. Wang S, Sakai H, Wiedmann M. 143.  1995. NAC covers ribosome-associated nascent chains thereby forming a protective environment for regions of nascent chains just emerging from the peptidyl transferase center. J. Cell Biol. 130:519–28 [Google Scholar]
  144. Wang Z, Jones JD, Rizo J, Gierasch LM. 144.  1993. Membrane-bound conformation of a signal peptide: a transferred nuclear Overhauser effect analysis. Biochemistry 32:13991–99 [Google Scholar]
  145. Weiche B, Burk J, Angelini S, Schiltz E, Thumfart JO, Koch H-G. 145.  2008. A cleavable N-terminal membrane anchor is involved in membrane binding of the Escherichia coli SRP receptor. J. Mol. Biol. 377:761–73 [Google Scholar]
  146. Wickner W. 146.  1995. The nascent-polypeptide-associated complex: having a “NAC” for fidelity in translocation. Proc. Natl. Acad. Sci. USA 92:9433–34 [Google Scholar]
  147. Willmund F, Del Alamo M, Pechmann S, Chen T, Albanèse V. 147.  et al. 2013. The cotranslational function of ribosome-associated Hsp70 in eukaryotic protein homeostasis. Cell 152:196–209 [Google Scholar]
  148. Wilson C, Connolly T, Morrison T, Gilmore R. 148.  1988. Integration of membrane proteins into the endoplasmic reticulum requires GTP. J. Cell Biol. 107:69–77 [Google Scholar]
  149. Woolhead CA, McCormick PJ, Johnson AE. 149.  2004. Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116:725–36 [Google Scholar]
  150. Xu D, Farmer A, Chook YM. 150.  2010. Recognition of nuclear targeting signals by Karyopherin-β proteins. Curr. Opin. Struct. Biol. 20:782–90 [Google Scholar]
  151. Yam AY, Xia Y, Lin H-TJ, Burlingame A, Gerstein M, Frydman J. 151.  2008. Defining the TriC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat. Struct. Mol. Biol. 15:1255–62 [Google Scholar]
  152. Zaher HS, Green R. 152.  2009. Quality control by the ribosome following peptide bond formation. Nature 457:161–66 [Google Scholar]
  153. Zhang D, Shan S. 153.  2012. Translation elongation regulates substrate selection by the signal recognition particle. J. Biol. Chem. 287:7652–60 [Google Scholar]
  154. Zhang X, Kung S, Shan S. 154.  2008. Demonstration of a multi-step mechanism for assembly of the SRP-SRP receptor complex: implications for the catalytic role of SRP RNA. J. Mol. Biol. 381:581–93 [Google Scholar]
  155. Zhang X, Lam VQ, Mou Y, Kimura T, Chung J. 155.  et al. 2011. Direct visualization reveals dynamics of a transient intermediate during protein assembly. Proc. Natl. Acad. Sci. USA 108:6450–55 [Google Scholar]
  156. Zhang X, Rashid R, Wang K, Shan S. 156.  2010. Sequential checkpoints govern fidelity during cotranslational protein targeting. Science 328:757–60 [Google Scholar]
  157. Zhang X, Schaffitzel C, Ban N, Shan S. 157.  2009. Multiple conformational changes in a GTPase complex regulate protein targeting. Proc. Natl. Acad. Sci. USA 106:1754–59 [Google Scholar]
  158. Zhang Y, Berndt U, Golz H, Tais A, Oellerer S. 158.  et al. 2012. NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum. Mol. Biol. Cell 23:3027–40 [Google Scholar]
  159. Zhang Z-R, Bonifacino JS, Hegde RS. 159.  2013. Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER. Cell 154:609–22 [Google Scholar]
  160. Zheng N, Gierasch LM. 160.  1996. Signal sequences: the same yet different. Cell 86:849–52 [Google Scholar]
  161. Zopf D, Bernstein HD, Johnson AE, Walter P. 161.  1990. The methionine-rich domain of the 54 kd protein subunit of the signal recognition particle contains an RNA binding site and can be crosslinked to a signal sequence. EMBO J. 9:4511–17 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error