1932

Abstract

ATP-binding cassette (ABC) transporters constitute one of the largest and most ancient protein superfamilies found in all living organisms. They function as molecular machines by coupling ATP binding, hydrolysis, and phosphate release to translocation of diverse substrates across membranes. The substrates range from vitamins, steroids, lipids, and ions to peptides, proteins, polysaccharides, and xenobiotics. ABC transporters undergo substantial conformational changes during substrate translocation. A comprehensive understanding of their inner workings thus requires linking these structural rearrangements to the different functional state transitions. Recent advances in single-particle cryogenic electron microscopy have not only delivered crucial information on the architecture of several medically relevant ABC transporters and their supramolecular assemblies, including the ATP-sensitive potassium channel and the peptide-loading complex, but also made it possible to explore the entire conformational space of these nanomachines under turnover conditions and thereby gain detailed mechanistic insights into their mode of action.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-011520-105201
2020-06-20
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/biochem/89/1/annurev-biochem-011520-105201.html?itemId=/content/journals/10.1146/annurev-biochem-011520-105201&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Rees DC, Johnson E, Lewinson O 2009. ABC transporters: the power to change. Nat. Rev. Mol. Cell Biol. 10:218–27
    [Google Scholar]
  2. 2. 
    Thomas C, Tampé R. 2018. Multifaceted structures and mechanisms of ABC transport systems in health and disease. Curr. Opin. Struct. Biol. 51:116–28
    [Google Scholar]
  3. 3. 
    Csanady L, Vergani P, Gadsby DC 2019. Structure, gating, and regulation of the CFTR anion channel. Physiol. Rev. 99:707–38
    [Google Scholar]
  4. 4. 
    Allikmets R. 1997. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat. Genet. 17:122
    [Google Scholar]
  5. 5. 
    Borst P, Elferink RO. 2002. Mammalian ABC transporters in health and disease. Annu. Rev. Biochem. 71:537–92
    [Google Scholar]
  6. 6. 
    Lee JY, Yang JG, Zhitnitsky D, Lewinson O, Rees DC 2014. Structural basis for heavy metal detoxification by an Atm1-type ABC exporter. Science 343:1133–36
    [Google Scholar]
  7. 7. 
    Srinivasan V, Pierik AJ, Lill R 2014. Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1. Science 343:1137–40
    [Google Scholar]
  8. 8. 
    Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM 2018. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat. Rev. Cancer 18:452–64
    [Google Scholar]
  9. 9. 
    Greene NP, Kaplan E, Crow A, Koronakis V 2018. Antibiotic resistance mediated by the MacB ABC transporter family: a structural and functional perspective. Front. Microbiol. 9:950
    [Google Scholar]
  10. 10. 
    McFarlane HE, Shin JJ, Bird DA, Samuels AL 2010. Arabidopsis ABCG transporters, which are required for export of diverse cuticular lipids, dimerize in different combinations. Plant Cell 22:3066–75
    [Google Scholar]
  11. 11. 
    Adebesin F, Widhalm JR, Boachon B, Lefevre F, Pierman B et al. 2017. Emission of volatile organic compounds from petunia flowers is facilitated by an ABC transporter. Science 356:1386–88
    [Google Scholar]
  12. 12. 
    Hwang JU, Song WY, Hong D, Ko D, Yamaoka Y et al. 2016. Plant ABC transporters enable many unique aspects of a terrestrial plant's lifestyle. Mol. Plant 9:338–55
    [Google Scholar]
  13. 13. 
    Hung LW, Wang IX, Nikaido K, Liu PQ, Ames GF, Kim SH 1998. Crystal structure of the ATP-binding subunit of an ABC transporter. Nature 396:703–7
    [Google Scholar]
  14. 14. 
    Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM et al. 2000. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101:789–800
    [Google Scholar]
  15. 15. 
    Smith PC, Karpowich N, Millen L, Moody JE, Rosen J et al. 2002. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol. Cell 10:139–49
    [Google Scholar]
  16. 16. 
    Walker JE, Saraste M, Runswick MJ, Gay NJ 1982. Distantly related sequences in the α- and β-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–51
    [Google Scholar]
  17. 17. 
    Vetter IR, Wittinghofer A. 1999. Nucleoside triphosphate-binding proteins: different scaffolds to achieve phosphoryl transfer. Q. Rev. Biophys. 32:1–56
    [Google Scholar]
  18. 18. 
    Seyffer F, Tampé R. 2015. ABC transporters in adaptive immunity. Biochim. Biophys. Acta Gen. Subj. 1850:449–60
    [Google Scholar]
  19. 19. 
    Oldham ML, Chen J. 2011. Snapshots of the maltose transporter during ATP hydrolysis. PNAS 108:15152–56
    [Google Scholar]
  20. 20. 
    Grossmann N, Vakkasoglu AS, Hulpke S, Abele R, Gaudet R, Tampé R 2014. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter. Nat. Commun. 5:5419
    [Google Scholar]
  21. 21. 
    Locher KP. 2016. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol. 23:487–93
    [Google Scholar]
  22. 22. 
    Karpowich N, Martsinkevich O, Millen L, Yuan YR, Dai PL et al. 2001. Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure 9:571–86
    [Google Scholar]
  23. 23. 
    Currier SJ, Kane SE, Willingham MC, Cardarelli CO, Pastan I, Gottesman MM 1992. Identification of residues in the first cytoplasmic loop of P-glycoprotein involved in the function of chimeric human MDR1-MDR2 transporters. J. Biol. Chem. 267:25153–59
    [Google Scholar]
  24. 24. 
    Cotten JF, Ostedgaard LS, Carson MR, Welsh MJ 1996. Effect of cystic fibrosis-associated mutations in the fourth intracellular loop of cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 271:21279–84
    [Google Scholar]
  25. 25. 
    Dawson RJ, Locher KP. 2006. Structure of a bacterial multidrug ABC transporter. Nature 443:180–85
    [Google Scholar]
  26. 26. 
    Loo TW, Bartlett MC, Clarke DM 2013. Human P-glycoprotein contains a greasy ball-and-socket joint at the second transmission interface. J. Biol. Chem. 288:20326–33
    [Google Scholar]
  27. 27. 
    Davidson AL, Dassa E, Orelle C, Chen J 2008. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol. Mol. Biol. Rev. 72:317–64
    [Google Scholar]
  28. 28. 
    ter Beek J, Guskov A, Slotboom DJ 2014. Structural diversity of ABC transporters. J. Gen. Physiol. 143:419–35
    [Google Scholar]
  29. 29. 
    Rempel S, Stanek WK, Slotboom DJ 2019. ECF-type ATP-binding cassette transporters. Annu. Rev. Biochem. 88:551–76
    [Google Scholar]
  30. 30. 
    Oldham ML, Khare D, Quiocho FA, Davidson AL, Chen J 2007. Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450:515–21
    [Google Scholar]
  31. 31. 
    Locher KP, Lee AT, Rees DC 2002. The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science 296:1091–98
    [Google Scholar]
  32. 32. 
    Korkhov VM, Mireku SA, Locher KP 2012. Structure of AMP-PNP-bound vitamin B12 transporter BtuCD–F. Nature 490:367–72
    [Google Scholar]
  33. 33. 
    Russell RR, Aduse-Opoku J, Sutcliffe IC, Tao L, Ferretti JJ 1992. A binding protein-dependent transport system in Streptococcus mutans responsible for multiple sugar metabolism. J. Biol. Chem. 267:4631–37
    [Google Scholar]
  34. 34. 
    Higgins CF, Ames GF. 1981. Two periplasmic transport proteins which interact with a common membrane receptor show extensive homology: complete nucleotide sequences. PNAS 78:6038–42
    [Google Scholar]
  35. 35. 
    Berntsson RP, Smits SH, Schmitt L, Slotboom DJ, Poolman B 2010. A structural classification of substrate-binding proteins. FEBS Lett 584:2606–17
    [Google Scholar]
  36. 36. 
    Bordignon E, Grote M, Schneider E 2010. The maltose ATP-binding cassette transporter in the 21st century–towards a structural dynamic perspective on its mode of action. Mol. Microbiol. 77:1354–66
    [Google Scholar]
  37. 37. 
    Quiocho FA, Ledvina PS. 1996. Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes. Mol. Microbiol. 20:17–25
    [Google Scholar]
  38. 38. 
    Xu K, Zhang M, Zhao Q, Yu F, Guo H et al. 2013. Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis. Nature 497:268–71
    [Google Scholar]
  39. 39. 
    Swier LJ, Guskov A, Slotboom DJ 2016. Structural insight in the toppling mechanism of an energy-coupling factor transporter. Nat. Commun. 7:11072
    [Google Scholar]
  40. 40. 
    Karpowich NK, Song JM, Cocco N, Wang DN 2015. ATP binding drives substrate capture in an ECF transporter by a release-and-catch mechanism. Nat. Struct. Mol. Biol. 22:565–71
    [Google Scholar]
  41. 41. 
    Wong K, Ma J, Rothnie A, Biggin PC, Kerr ID 2014. Towards understanding promiscuity in multidrug efflux pumps. Trends Biochem. Sci. 39:8–16
    [Google Scholar]
  42. 42. 
    Ward A, Reyes CL, Yu J, Roth CB, Chang G 2007. Flexibility in the ABC transporter MsbA: alternating access with a twist. PNAS 104:19005–10
    [Google Scholar]
  43. 43. 
    Mi W, Li Y, Yoon SH, Ernst RK, Walz T, Liao M 2017. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature 549:233–37
    [Google Scholar]
  44. 44. 
    Patlak CS. 1957. Contributions to the theory of active transport: II. The gate type non-carrier mechanism and generalizations concerning tracer flow, efficiency, and measurement of energy expenditure. Bull. Math. Biophys. 19:209–35
    [Google Scholar]
  45. 45. 
    Vidaver GA. 1966. Inhibition of parallel flux and augmentation of counter flux shown by transport models not involving a mobile carrier. J. Theor. Biol. 10:301–6
    [Google Scholar]
  46. 46. 
    Jardetzky O. 1966. Simple allosteric model for membrane pumps. Nature 211:969–70
    [Google Scholar]
  47. 47. 
    Lauger P. 1979. A channel mechanism for electrogenic ion pumps. Biochim. Biophys. Acta Biomembr. 552:143–61
    [Google Scholar]
  48. 48. 
    Hofmann S, Januliene D, Mehdipour AR, Thomas C, Stefan E et al. 2019. Conformation space of a heterodimeric ABC exporter under turnover conditions. Nature 571:580–83
    [Google Scholar]
  49. 49. 
    Dean M, Annilo T. 2005. Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu. Rev. Genom. Hum. Genet. 6:123–42
    [Google Scholar]
  50. 50. 
    Gerovac M, Tampé R. 2019. Control of mRNA translation by versatile ATP-driven machines. Trends Biochem. Sci. 44:167–80
    [Google Scholar]
  51. 51. 
    Quazi F, Lenevich S, Molday RS 2012. ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat. Commun. 3:925
    [Google Scholar]
  52. 52. 
    Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M et al. 2012. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat. Genet. 44:1152–55
    [Google Scholar]
  53. 53. 
    Puljung MC. 2018. Cryo-electron microscopy structures and progress toward a dynamic understanding of KATP channels. J. Gen. Physiol. 150:653–69
    [Google Scholar]
  54. 54. 
    Babenko AP, Aguilar-Bryan L, Bryan J 1998. A view of SUR/KIR6.x, KATP channels. Annu. Rev. Physiol. 60:667–87
    [Google Scholar]
  55. 55. 
    Mittra R, Coyle EM, Callaghan R 2016. Just how and where does P-glycoprotein bind all those drugs?. ABC Transporters—40 Years On AM George 153–94 Cham, Switz: Springer
    [Google Scholar]
  56. 56. 
    Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM 1999. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39:361–98
    [Google Scholar]
  57. 57. 
    Gottesman MM, Pastan I. 1993. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62:385–427
    [Google Scholar]
  58. 58. 
    Jin MS, Oldham ML, Zhang Q, Chen J 2012. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature 490:566–69
    [Google Scholar]
  59. 59. 
    Li J, Jaimes KF, Aller SG 2014. Refined structures of mouse P-glycoprotein. Protein Sci 23:34–46
    [Google Scholar]
  60. 60. 
    Hrycyna CA, Ramachandra M, Ambudkar SV, Ko YH, Pedersen PL et al. 1998. Mechanism of action of human P-glycoprotein ATPase activity: Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites. J. Biol. Chem. 273:16631–34
    [Google Scholar]
  61. 61. 
    Urbatsch IL, Sankaran B, Weber J, Senior AE 1995. P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J. Biol. Chem. 270:19383–90
    [Google Scholar]
  62. 62. 
    Bruggemann EP, Currier SJ, Gottesman MM, Pastan I 1992. Characterization of the azidopine and vinblastine binding site of P-glycoprotein. J. Biol. Chem. 267:21020–26
    [Google Scholar]
  63. 63. 
    Dey S, Ramachandra M, Pastan I, Gottesman MM, Ambudkar SV 1997. Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. PNAS 94:10594–99
    [Google Scholar]
  64. 64. 
    Loo TW, Clarke DM. 2001. Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil. J. Biol. Chem. 276:14972–79
    [Google Scholar]
  65. 65. 
    Loo TW, Clarke DM. 2002. Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein. J. Biol. Chem. 277:44332–38
    [Google Scholar]
  66. 66. 
    Chufan EE, Kapoor K, Sim HM, Singh S, Talele TT et al. 2013. Multiple transport-active binding sites are available for a single substrate on human P-glycoprotein (ABCB1). PLOS ONE 8:e82463
    [Google Scholar]
  67. 67. 
    Esser L, Zhou F, Pluchino KM, Shiloach J, Ma J et al. 2017. Structures of the multidrug transporter P-glycoprotein reveal asymmetric ATP binding and the mechanism of polyspecificity. J. Biol. Chem. 292:446–61
    [Google Scholar]
  68. 68. 
    Kim Y, Chen J. 2018. Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation. Science 359:915–19
    [Google Scholar]
  69. 69. 
    al-Shawi MK, Senior AE. 1993. Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein. J. Biol. Chem. 268:4197–206
    [Google Scholar]
  70. 70. 
    Ambudkar SV. 1998. Drug-stimulatable ATPase activity in crude membranes of human MDR1-transfected mammalian cells. Methods Enzymol 292:504–14
    [Google Scholar]
  71. 71. 
    Sarkadi B, Price EM, Boucher RC, Germann UA, Scarborough GA 1992. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J. Biol. Chem. 267:4854–58
    [Google Scholar]
  72. 72. 
    Dastvan R, Mishra S, Peskova YB, Nakamoto RK, McHaourab HS 2019. Mechanism of allosteric modulation of P-glycoprotein by transport substrates and inhibitors. Science 364:689–92
    [Google Scholar]
  73. 73. 
    Cole SP. 2014. Targeting multidrug resistance protein 1 (MRP1, ABCC1): past, present, and future. Annu. Rev. Pharmacol. Toxicol. 54:95–117
    [Google Scholar]
  74. 74. 
    Johnson ZL, Chen J. 2017. Structural basis of substrate recognition by the multidrug resistance protein MRP1. Cell 168:1075–85.e9
    [Google Scholar]
  75. 75. 
    Johnson ZL, Chen J. 2018. ATP binding enables substrate release from multidrug resistance protein 1. Cell 172:81–89.e10
    [Google Scholar]
  76. 76. 
    Bakos E, Evers R, Szakacs G, Tusnady GE, Welker E et al. 1998. Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain. J. Biol. Chem. 273:32167–75
    [Google Scholar]
  77. 77. 
    Bakos E, Evers R, Calenda G, Tusnady GE, Szakacs G et al. 2000. Characterization of the amino-terminal regions in the human multidrug resistance protein (MRP1). J. Cell Sci. 113:Part 244451–61
    [Google Scholar]
  78. 78. 
    Westlake CJ, Qian YM, Gao M, Vasa M, Cole SP, Deeley RG 2003. Identification of the structural and functional boundaries of the multidrug resistance protein 1 cytoplasmic loop 3. Biochemistry 42:14099–113
    [Google Scholar]
  79. 79. 
    Riordan JR. 2008. CFTR function and prospects for therapy. Annu. Rev. Biochem. 77:701–26
    [Google Scholar]
  80. 80. 
    Zhang Z, Chen J. 2016. Atomic structure of the cystic fibrosis transmembrane conductance regulator. Cell 167:1586–97.e9
    [Google Scholar]
  81. 81. 
    Liu F, Zhang Z, Csanady L, Gadsby DC, Chen J 2017. Molecular structure of the human CFTR ion channel. Cell 169:85–95.e8
    [Google Scholar]
  82. 82. 
    Zhang Z, Liu F, Chen J 2017. Conformational changes of CFTR upon phosphorylation and ATP binding. Cell 170:483–91.e8
    [Google Scholar]
  83. 83. 
    Zhang Z, Liu F, Chen J 2018. Molecular structure of the ATP-bound, phosphorylated human CFTR. PNAS 115:12757–62
    [Google Scholar]
  84. 84. 
    Liu F, Zhang Z, Levit A, Levring J, Touhara KK et al. 2019. Structural identification of a hotspot on CFTR for potentiation. Science 364:1184–88
    [Google Scholar]
  85. 85. 
    Shintre CA, Pike AC, Li Q, Kim JI, Barr AJ et al. 2013. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. PNAS 110:9710–15
    [Google Scholar]
  86. 86. 
    Xu D, Feng Z, Hou WT, Jiang YL, Wang L et al. 2019. Cryo-EM structure of human lysosomal cobalamin exporter ABCD4. Cell Res 29:1039–41
    [Google Scholar]
  87. 87. 
    Shani N, Jimenez-Sanchez G, Steel G, Dean M, Valle D 1997. Identification of a fourth half ABC transporter in the human peroxisomal membrane. Hum. Mol. Genet. 6:1925–31
    [Google Scholar]
  88. 88. 
    Morita M, Imanaka T. 2012. Peroxisomal ABC transporters: structure, function and role in disease. Biochim. Biophys. Acta Mol. Basis Dis. 1822:1387–96
    [Google Scholar]
  89. 89. 
    van Roermund CW, Visser WF, Ijlst L, van Cruchten A, Boek M et al. 2008. The human peroxisomal ABC half transporter ALDP functions as a homodimer and accepts acyl-CoA esters. FASEB J 22:4201–8
    [Google Scholar]
  90. 90. 
    van Roermund CW, Visser WF, Ijlst L, Waterham HR, Wanders RJ 2011. Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid β-oxidation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1811:148–52
    [Google Scholar]
  91. 91. 
    van Roermund CW, Ijlst L, Wagemans T, Wanders RJ, Waterham HR 2014. A role for the human peroxisomal half-transporter ABCD3 in the oxidation of dicarboxylic acids. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1841:563–68
    [Google Scholar]
  92. 92. 
    Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R et al. 1993. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 361:726–30
    [Google Scholar]
  93. 93. 
    Ferdinandusse S, Jimenez-Sanchez G, Koster J, Denis S, Van Roermund CW et al. 2015. A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum. Mol. Genet. 24:361–70
    [Google Scholar]
  94. 94. 
    Lee JY, Kinch LN, Borek DM, Wang J, Wang J et al. 2016. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature 533:561–64
    [Google Scholar]
  95. 95. 
    Lin DY, Huang S, Chen J 2015. Crystal structures of a polypeptide processing and secretion transporter. Nature 523:425–30
    [Google Scholar]
  96. 96. 
    Oldham ML, Chen J. 2011. Crystal structure of the maltose transporter in a pretranslocation intermediate state. Science 332:1202–5
    [Google Scholar]
  97. 97. 
    Kieuvongngam V, Olinares PDB, Palillo A, Oldham ML, Chait BT, Chen J 2020. Structural basis of substrate recognition by a polypeptide processing and secretion transporter. eLife 9:e51492
    [Google Scholar]
  98. 98. 
    Robey RW, To KK, Polgar O, Dohse M, Fetsch P et al. 2009. ABCG2: a perspective. Adv. Drug Deliv. Rev. 61:3–13
    [Google Scholar]
  99. 99. 
    Taylor NMI, Manolaridis I, Jackson SM, Kowal J, Stahlberg H, Locher KP 2017. Structure of the human multidrug transporter ABCG2. Nature 546:504–9
    [Google Scholar]
  100. 100. 
    Jackson SM, Manolaridis I, Kowal J, Zechner M, Taylor NMI et al. 2018. Structural basis of small-molecule inhibition of human multidrug transporter ABCG2. Nat. Struct. Mol. Biol. 25:333–40
    [Google Scholar]
  101. 101. 
    Manolaridis I, Jackson SM, Taylor NMI, Kowal J, Stahlberg H, Locher KP 2018. Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states. Nature 563:426–30
    [Google Scholar]
  102. 102. 
    Srikant S, Gaudet R. 2019. Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters. Nat. Struct. Mol. Biol. 26:792–801
    [Google Scholar]
  103. 103. 
    Qian H, Zhao X, Cao P, Lei J, Yan N, Gong X 2017. Structure of the human lipid exporter ABCA1. Cell 169:1228–39.e10
    [Google Scholar]
  104. 104. 
    Perez C, Gerber S, Boilevin J, Bucher M, Darbre T et al. 2015. Structure and mechanism of an active lipid-linked oligosaccharide flippase. Nature 524:433–38
    [Google Scholar]
  105. 105. 
    Perez C, Mehdipour AR, Hummer G, Locher KP 2019. Structure of outward-facing PglK and molecular dynamics of lipid-linked oligosaccharide recognition and translocation. Structure 27:669–78.e5
    [Google Scholar]
  106. 106. 
    Bi Y, Mann E, Whitfield C, Zimmer J 2018. Architecture of a channel-forming O-antigen polysaccharide ABC transporter. Nature 553:361–65
    [Google Scholar]
  107. 107. 
    Caffalette CA, Corey RA, Sansom MSP, Stansfeld PJ, Zimmer J 2019. A lipid gating mechanism for the channel-forming O antigen ABC transporter. Nat. Commun. 10:824
    [Google Scholar]
  108. 108. 
    Luo Q, Yang X, Yu S, Shi H, Wang K et al. 2017. Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG. Nat. Struct. Mol. Biol. 24:469–74
    [Google Scholar]
  109. 109. 
    Dong H, Zhang Z, Tang X, Paterson NG, Dong C 2017. Structural and functional insights into the lipopolysaccharide ABC transporter LptB2FG. Nat. Commun. 8:222
    [Google Scholar]
  110. 110. 
    Li Y, Orlando BJ, Liao M 2019. Structural basis of lipopolysaccharide extraction by the LptB2FGC complex. Nature 567:486–90
    [Google Scholar]
  111. 111. 
    Owens TW, Taylor RJ, Pahil KS, Bertani BR, Ruiz N et al. 2019. Structural basis of unidirectional export of lipopolysaccharide to the cell surface. Nature 567:550–53
    [Google Scholar]
  112. 112. 
    Du D, Wang-Kan X, Neuberger A, van Veen HW, Pos KM et al. 2018. Multidrug efflux pumps: structure, function and regulation. Nat. Rev. Microbiol. 16:523–39
    [Google Scholar]
  113. 113. 
    Fitzpatrick AWP, Llabres S, Neuberger A, Blaza JN, Bai XC et al. 2017. Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nat. Microbiol. 2:17070
    [Google Scholar]
  114. 114. 
    Okada U, Yamashita E, Neuberger A, Morimoto M, van Veen HW, Murakami S 2017. Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii. Nat. Commun 8:1336
    [Google Scholar]
  115. 115. 
    Crow A, Greene NP, Kaplan E, Koronakis V 2017. Structure and mechanotransmission mechanism of the MacB ABC transporter superfamily. PNAS 114:12572–77
    [Google Scholar]
  116. 116. 
    Koch J, Guntrum R, Heintke S, Kyritsis C, Tampé R 2004. Functional dissection of the transmembrane domains of the transporter associated with antigen processing (TAP). J. Biol. Chem. 279:10142–47
    [Google Scholar]
  117. 117. 
    Demirel O, Jan I, Wolters D, Blanz J, Saftig P et al. 2012. The lysosomal polypeptide transporter TAPL is stabilized by interaction with LAMP-1 and LAMP-2. J. Cell Sci. 125:4230–40
    [Google Scholar]
  118. 118. 
    Nichols CG. 2006. KATP channels as molecular sensors of cellular metabolism. Nature 440:470–76
    [Google Scholar]
  119. 119. 
    Li N, Wu JX, Ding D, Cheng J, Gao N, Chen L 2017. Structure of a pancreatic ATP-sensitive potassium channel. Cell 168:101–10.e10
    [Google Scholar]
  120. 120. 
    Martin GM, Yoshioka C, Rex EA, Fay JF, Xie Q et al. 2017. Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating. eLife 6:e24149
    [Google Scholar]
  121. 121. 
    Martin GM, Kandasamy B, DiMaio F, Yoshioka C, Shyng SL 2017. Anti-diabetic drug binding site in a mammalian KATP channel revealed by cryo-EM. eLife 6:e31054
    [Google Scholar]
  122. 122. 
    Lee KPK, Chen J, MacKinnon R 2017. Molecular structure of human KATP in complex with ATP and ADP. eLife 6:e32481
    [Google Scholar]
  123. 123. 
    Wu JX, Ding D, Wang M, Kang Y, Zeng X, Chen L 2018. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels. Protein Cell 9:553–67
    [Google Scholar]
  124. 124. 
    Ding D, Wang M, Wu JX, Kang Y, Chen L 2019. The structural basis for the binding of repaglinide to the pancreatic KATP channel. Cell Rep 27:1848–57.e4
    [Google Scholar]
  125. 125. 
    Oldham ML, Hite RK, Steffen AM, Damko E, Li Z et al. 2016. A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter. Nature 529:537–40
    [Google Scholar]
  126. 126. 
    Ho H, Miu A, Alexander MK, Garcia NK, Oh A et al. 2018. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature 557:196–201
    [Google Scholar]
  127. 127. 
    Martin GM, Sung MW, Yang Z, Innes LM, Kandasamy B et al. 2019. Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM. eLife 8:e46417
    [Google Scholar]
  128. 128. 
    Trowitzsch S, Tampé R. 2018. ABC transporters in dynamic macromolecular assemblies. J. Mol. Biol. 430:4481–95
    [Google Scholar]
  129. 129. 
    Abele R, Tampé R. 2018. Moving the cellular peptidome by transporters. Front. Cell Dev. Biol. 6:43
    [Google Scholar]
  130. 130. 
    Blum JS, Wearsch PA, Cresswell P 2013. Pathways of antigen processing. Annu. Rev. Immunol. 31:443–73
    [Google Scholar]
  131. 131. 
    Thomas C, Tampé R. 2019. MHC I chaperone complexes shaping immunity. Curr. Opin. Immunol. 58:9–15
    [Google Scholar]
  132. 132. 
    Thomas C, Tampé R. 2017. Proofreading of peptide-MHC complexes through dynamic multivalent interactions. Front. Immunol. 8:65
    [Google Scholar]
  133. 133. 
    Neerincx A, Boyle LH. 2017. Properties of the tapasin homologue TAPBPR. Curr. Opin. Immunol. 46:97–102
    [Google Scholar]
  134. 134. 
    Thomas C, Tampé R. 2017. Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing. Science 358:1060–64
    [Google Scholar]
  135. 135. 
    Jiang J, Natarajan K, Boyd LF, Morozov GI, Mage MG, Margulies DH 2017. Crystal structure of a TAPBPR-MHC I complex reveals the mechanism of peptide editing in antigen presentation. Science 358:1064–68
    [Google Scholar]
  136. 136. 
    Mayerhofer PU, Tampé R. 2015. Antigen translocation machineries in adaptive immunity and viral immune evasion. J. Mol. Biol. 427:1102–18
    [Google Scholar]
  137. 137. 
    Oldham ML, Grigorieff N, Chen J 2016. Structure of the transporter associated with antigen processing trapped by herpes simplex virus. eLife 5:e21829
    [Google Scholar]
  138. 138. 
    Hulpke S, Tomioka M, Kremmer E, Ueda K, Abele R, Tampé R 2012. Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex. Cell Mol. Life Sci. 69:3317–27
    [Google Scholar]
  139. 139. 
    Blees A, Januliene D, Hofmann T, Koller N, Schmidt C et al. 2017. Structure of the human MHC-I peptide-loading complex. Nature 551:525–28
    [Google Scholar]
  140. 140. 
    Zutz A, Hoffmann J, Hellmich UA, Glaubitz C, Ludwig B et al. 2011. Asymmetric ATP hydrolysis cycle of the heterodimeric multidrug ABC transport complex TmrAB from Thermus thermophilus. J. Biol. Chem 286:7104–15
    [Google Scholar]
  141. 141. 
    Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB et al. 2015. Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature 517:396–400
    [Google Scholar]
  142. 142. 
    Nöll A, Thomas C, Herbring V, Zollmann T, Barth K et al. 2017. Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP. PNAS 114:E438–47
    [Google Scholar]
  143. 143. 
    Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S et al. 2014. Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. PNAS 111:9145–50
    [Google Scholar]
  144. 144. 
    Hutter CAJ, Timachi MH, Hurlimann LM, Zimmermann I, Egloff P et al. 2019. The extracellular gate shapes the energy profile of an ABC exporter. Nat. Commun. 10:2260
    [Google Scholar]
  145. 145. 
    Cheng Y. 2018. Single-particle cryo-EM—How did it get here and where will it go. Science 361:876–80
    [Google Scholar]
  146. 146. 
    Renaud JP, Chari A, Ciferri C, Liu WT, Remigy HW et al. 2018. Cryo-EM in drug discovery: achievements, limitations and prospects. Nat. Rev. Drug Discov. 17:471–92
    [Google Scholar]
  147. 147. 
    Cheng Y. 2018. Membrane protein structural biology in the era of single particle cryo-EM. Curr. Opin. Struct. Biol. 52:58–63
    [Google Scholar]
  148. 148. 
    Scapin G, Potter CS, Carragher B 2018. Cryo-EM for small molecules discovery, design, understanding, and application. Cell Chem. Biol. 25:1318–25
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-011520-105201
Loading
/content/journals/10.1146/annurev-biochem-011520-105201
Loading

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