Cystic fibrosis transmembrane conductance regulator (CFTR):closedandopenstate channelmodels

Journal of Biological Chemistry

Volumn 290, Issue 38, 2015, Pages 22891-22906

  Corradi, Valentina ^a   Vergani, Paola ^b   Tieleman, D Peter ^a  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

NEGATIVE IONS; OPEN CHANNEL FLOW;

ATP BINDING CASSETTE TRANSPORTERS; CONFORMATIONAL STATE; CONFORMATIONAL TRANSITIONS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATORS; HOMOLOGY MODELING; NUCLEOTIDE-BINDING DOMAIN; STRUCTURAL INFORMATION; TRANSMEMBRANE DOMAIN;

BINS;

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATE; ANION CHANNEL; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; NUCLEOTIDE; CFTR PROTEIN, HUMAN; RECOMBINANT PROTEIN;

APICAL MEMBRANE; ARTICLE; BINDING SITE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYSTIC FIBROSIS; GENE MUTATION; GENETIC CODE; HUMAN; HYDROLYSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN STRUCTURE; SEQUENCE ALIGNMENT; CHANNEL GATING; CHEMICAL MODEL; CHEMISTRY; GENETICS; METABOLISM; PROTEIN TERTIARY STRUCTURE; STRUCTURAL HOMOLOGY;

CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMANS; ION CHANNEL GATING; MODELS, CHEMICAL; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS; STRUCTURAL HOMOLOGY, PROTEIN;

EID: 84943189754     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.665125     Document Type: Article

References (114)

1. Rommens, J. M., Iannuzzi, M. C, Kerem, B., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy, D., Hidaka, N, et al. (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245, 1059-1065
2. Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O'Riordan, C. R., and Smith, A. E. (1990) Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63, 827-834
3. Dalemans, W., Barbry, P., Champigny, G., Jallat, S., Dott, K., Dreyer, D., Crystal, R. G., Pavirani, A., Lecocq, J. P., and Lazdunski, M. (1991) Altered chloride ion channel kinetics associated with the AF508 cystic fibrosis mutation. Nature 354, 526-528
4. Gadsby, D. C, Vergani, P., and Csanády, L. (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477-483
5. Riordan, J. R. (2005) Assembly of functional CFTR chloride channels. Annu. Rev. Physiol. 67, 701-718
6. O'Sullivan, B. P., and Freedman, S. D. (2009) Cystic fibrosis. Lancet 373, 1891-1904
7. Sloane, P. A., Shastry, S., Wilhelm, A., Courville, C, Tang, L. P., Backer, K., Levin, E., Raju, S. V., Li, Y., Mazur, M., Byan-Parker, S., Grizzle, W., Sorscher, E. J., Dransfield, M. T., and Rowe, S. M. (2012) A pharmacologic approach to acquired cystic fibrosis transmembrane conductance regulator dysfunction in smoking related lung disease. PLoS ONE 7, e39809
8. Thiagarajah, J. R., and Verkman, A. S. (2012) CFTR inhibitors for treating diarrheal disease. Clin. Pharmacol. Ther. 92, 287-290
9. Solymosi, E. A., Kaestle-Gembardt, S. M., Vadász, I., Wang, L., Neye, N, Chupin, C J., Rozowsky, S., Ruehl, R., Tabuchi, A., Schulz, H., Kapus, A., Morty, R. E., and Kuebler, W. M. (2013) Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema. Proc. Natl. Acad. Sci. U. S. A. 110, E2308-E2316
10. Xu, J., Yong, M., Li, J., Dong, X., Yu, T., Fu, X., and Hu, L. (2015) High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo. Oncol. Rep. 33, 2227-2234
11. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N, Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., et al. (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073
12. Holland, I. B., Cole, S. P., Kuchler, K., and Higgins, C. F. (eds) (2003) ABC Proteins: From Bacteria to Man, Academic Press, Amsterdam, The Netherlands
13. Biemans-Oldehinkel, E., Doeven, M. K., and Poolman, B. (2006) ABC transporter architecture and regulatory roles of accessory domains. FEBS Lett. 580, 1023-1035
14. Dawson, R. J., and Locher, K. P. (2006) Structure of abacterial multidrug ABC transporter. Nature 443, 180-185
15. Ward, A., Reyes, C. L., Yu, J., Roth, C. B., and Chang, G. (2007) Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc. Natl. Acad. Sci. U. S. A. 104, 19005-19010
16. Hohl, M., Briand, C, Grütter, M. G., and Seeger, M. A. (2012) Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat Struct. Mol. Biol. 19, 395-402
17. Procko, E., O'Mara, M. L., Bennett, W. F., Tieleman, D. P., and Gaudet, R. (2009) The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEBJ. 23, 1287-1302
18. Basso, C, Vergani, P., Nairn, A. C, and Gadsby, D. C. (2003) Prolonged nonhydrolytic interaction of nucleotide with CFTR's NH2-terminal nucleotide binding domain and its role in channel gating. J. Gen. Physiol. 122, 333-348
19. Aleksandrov, L., Aleksandrov, A. A., Chang, X. B., and Riordan, J. R. (2002) The first nucleotide binding domain of cystic fibrosis transmembrane conductance regulator is a site of stable nucleotide interaction, whereas the second is a site of rapid turnover. J. Biol. Chem. 277, 15419-15425
20. Hegedus, T., Aleksandrov, A., Mengos, A., Cui, L., Jensen, T. J., and Riordan, J. R. (2009) Role of individual R domain phosphorylation sites in CFTR regulation by protein kinase A. Biochim. Biophys. Acta 1788, 1341-1349
21. Vergani, P., Lockless, S. W., Nairn, A. C, and Gadsby, D. C. (2005) CFTR channel opening by ATP-driven tight dimerization of its nucleotidebinding domains. Nature 433, 876-880
22. - ion pore revealed by distributions of open channel burst durations. Proc. Natl. Acad. Sci. U. S. A. 107, 1241-1246
23. - channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol. 587, 2151-2161
24. Vergani, P., Nairn, A. C, and Gadsby, D. C (2003) On the mechanism of MgATP-dependent gating of CFTR CT channels. J. Gen. Physiol. 121, 17-36
25. Zhou, Z., Wang, X., Liu, H. Y., Zou, X., Li, M., and Hwang, T. C. (2006) The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics. J. Gen. Physiol. 128, 413-422
26. Lewis, H. A., Wang, C, Zhao, X., Hamuro, Y., Conners, K., Kearins, M. C, Lu, F., Sauder, J. M., Molnar, K. S., Coales, S. J., Maloney, P. C, Guggino, W. B., Wetmore, D. R., Weber, P. C, and Hunt, J. F. (2010) Structure and dynamics of NBD1 from CFTR characterized using crystallography and hydrogen/deuterium exchange mass spectrometry. J. Mol. Biol. 396, 406-430
27. Thibodeau, P. H, Brautigam, C. A., Machius, M., and Thomas, P. J. (2005) Side chain and backbone contributions of Phe-508 to CFTR folding. Nat Struct. Mol. Biol. 12, 10-16
28. Mendoza, J. L., Schmidt, A., Li, Q., Nuvaga, E., Barrett, T., Bridges, R. J., Feranchak, A. P., Brautigam, C. A., and Thomas, P. J. (2012) Requirements for efficient correction of AF508 CFTR revealed by analyses of evolved sequences. Cell 148, 164-174
29. Lewis, H. A., Buchanan, S. G., Burley, S. K., Conners, K., Dickey, M., Dorwart, M., Fowler, R., Gao, X., Guggino, W. B., Hendrickson, W. A., Hunt, J. F., Kearins, M. C, Lorimer, D., Maloney, P. C, Post, K. W., et al. (2004) Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. EMBOJ. 23, 282-293
30. Lewis, H. A., Zhao, X., Wang, C, Sauder, J. M., Rooney, I., Noland, B. W., Lorimer, D., Kearins, M. C, Conners, K., Condon, B., Maloney, P. C, Guggino, W. B., Hunt, J. F., and Emtage, S. (2005) Impact of the AF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J. Biol. Chem. 280, 1346-1353
31. Atwell, S., Brouillette, C. G., Conners, K., Emtage, S., Gheyi, T., Guggino, W. B., Hendle, J., Hunt, J. F., Lewis, H. A., Lu, F., Protasevich, I. I., Rodgers, L. A., Romero, R., Wasserman, S. R., Weber, P. C, et al. (2010) Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant. Protein Eng Des. Sel. 23, 375-384
32. Rahman, K. S., Cui, G., Harvey, S. C, and McCarty, N. A. (2013) Modeling the conformational changes underlying channel opening in CFTR. PLoS ONE 8, e74574
33. Mornon, J. P., Lehn, P., and Callebaut, I. (2008) Atomic model of human cystic fibrosis transmembrane conductance regulator: membrane-spanning domains and coupling interfaces. Cell. Mol. Life Sci. 65, 2594-2612
34. Mornon, J. P., Lehn, P., and Callebaut, I. (2009) Molecular models of the open and closed states of the whole human CFTR protein. Cell. Mol. Life Sci. 66, 3469-3486
35. Dalton, J., Kalid, O., Schushan, M., Ben-Tal, N., and Villà-Freixa, J. (2012) Newmodel of cystic fibrosis transmembrane conductance regulator proposes active channel-like conformation. J. Chem. Inf. Model. 52, 1842-1853
36. Serohijos, A. W., Hegedus, T., Aleksandrov, A. A., He, L., Cui, L., Dokholyan, N. V., and Riordan, J. R. (2008) Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function. Proc. Natl. Acad. Sci. U. S. A. 105, 3256-3261
37. Alexander, C, Ivetac, A., Liu, X., Norimatsu, Y., Serrano, J. R., Landstrom, A., Sansom, M., and Dawson, D. C. (2009) Cystic fibrosis transmembrane conductance regulator: using differential reactivity toward channel-permeant and channel-impermeant thiol-reactive probes to test a molecular model for the pore. Biochemistry 48, 10078-10088
38. Norimatsu, Y., Ivetac, A., Alexander, C, Kirkham, J., O'Donnell, N., Dawson, D. C, and Sansom, M. S. (2012) Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore. Biochemistry 51, 2199-2212
39. Mendoza, J. L., and Thomas, P. J. (2007) Building an understanding of cystic fibrosis on the foundation of ABC transporter structures. J. Bioenerg. Biomembr. 39, 499-505
40. La Rusch, J., Jung, J., General, I. J., Lewis, M. D., Park, H. W., Brand, R. E., Gelrud, A., Anderson, M. A., Banks, P. A., Conwell, D., Lawrence, C, Romagnuolo, J., Baillie, J., Alkaade, S., Cote, G., et al. (2014) Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. Plos Genet. 10, e1004376
41. Mornon, J. P., Hoffmann, B., Jonic, S., Lehn, P., and Callebaut, I. (2015) Full-open and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics. Cell. Mol. Life Sci. 72, 1377-1403
42. Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., and Chang, G. (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323, 1718-1722
43. Li, J., Jaimes, K. F., and Aller, S. G. (2014) Refined structures of mouse P-glycoprotein. Protein Sci. 23, 34-46
44. Shintre, C. A., Pike, A. C, Li, Q., Kim, J. I., Barr, A. J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., Stansfeld, P. J., Sansom, M. S., Edwards, A. M., Bountra, C, Marsden, B. D., et al. (2013) Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proc. Natl. Acad. Sci. U. S. A. 110, 9710-9715
45. Choudhury, H. G., Tong, Z., Mathavan, I., Li, Y., Iwata, S., Zirah, S., Rebuffat, S., Van Veen, H. W., and Beis, K. (2014) Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc. Natl. Acad. Sci. U. S. A. 111, 9145-9150
46. Hyde, B. B., Liesa, M., Elorza, A. A., Qiu, W., Haigh, S. E., Richey, L., Mikkola, H. K., Schlaeger, T. M., and Shirihai, O. S. (2012) The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo. Cell Death Differ. 19, 1117-1126
47. Young, L., Leonhard, K., Tatsuta, T., Trowsdale, J., and Langer, T. (2001) Role of the ABC transporter Mdl1 in peptide export from mitochondria. Science 291, 2135-2138
48. Velamakanni, S., Yao, Y., Gutmann, D. A., and Van Veen, H. W. (2008) Multidrug transport by the ABC transporter Sav 1866 from Staphylococcus aureus. Biochemistry 47, 9300-9308
49. Woebking, B., Reuter, G., Shilling, R. A., Velamakanni, S., Shahi, S., Venter, H., Balakrishnan, L., and Van Veen, H. W. (2005) Drug-lipid A interactions on the Escherichia coli ABC transporter MsbA. J. Bacteriol. 187, 6363-6369
50. Martin, C., Berridge, G., Higgins, C. F., Mistry, P., Charlton, P., and Callaghan, R. (2000) Communication between multiple drug binding sites on P-glycoprotein. Mol. Pharmacol. 58, 624-632
51. Chufan, E. E., Kapoor, K., Sim, H. M., Singh, S., Talele, T. T., Durell, S. R., and Ambudkar, S. V. (2013) Multiple transport-active binding sites are available for a single substrate on human P-glycoprotein (ABCB1). PLoS ONE 8, e82463
52. Sharom, F. J. (2008) ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 9, 105-127
53. Csanády, L., Mihályi, C., Szollosi, A., Töröcsik, B., and Vergani, P. (2013) Conformational changes in the catalytically inactive nucleotide-binding site of CFTR. J. Gen. Physiol. 142, 61-73
54. Chaves, L. A., and Gadsby, D. C. (2015) Cysteine accessibility probes timing and extent of NBD separation along the dimer interface in gating CFTR channels. J. Gen. Physiol. 145, 261-283
55. Tsai, M. F., Li, M., and Hwang, T. C. (2010) Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel. J. Gen. Physiol. 135, 399-414
56. Szollosi, A., Muallem, D. R., Csanády, L., and Vergani, P. (2011) Mutant cycles at CFTR's non-canonical ATP-binding site support little interface separation during gating. J. Gen. Physiol. 137, 549-562
57. Armougom, F., Moretti, S., Poirot, O., Audic, S., Dumas, P., Schaeli, B., Keduas, V., and Notredame, C. (2006) Expresso: automatic incorporation of structural information in multiple sequence alignments using 3D-coffee. Nucleic Acids Res. 34, W604-W608
58. Katoh, K., Misawa, K., Kuma, K., and Miyata, T. (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 30, 3059-3066
59. Sali, A., and Blundell, T. L. (1993) Comparative protein modeling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815
60. Cui, G., Zhang, Z. R., O'Brien, A. R., Song, B., and McCarty, N. A. (2008) Mutations at arginine 352 alter the pore architecture of CFTR. J. Membr. Biol. 222, 91-106
61. Cotten, J. F., and Welsh, M. J. (1999) Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge. J. Biol. Chem. 274, 5429-5435
62. Corradi, V., Singh, G., and Tieleman, D. P. (2012) The human transporter associated with antigen processing: molecular models to describe peptide binding competent states. J. Biol. Chem. 287, 28099-28111
63. Berendsen, H. J., Vanderspoel, D., and Vandrunen, R. (1995) Gromacs-a message-passing parallel molecular-dynamics implementation. Comput. Phys. Commun. 91, 43-56
64. Hess, B., Kutzner, C., Van Der Spoel, D., and Lindahl, E. (2008) GRO-MACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447
65. Schmid, N., Eichenberger, A. P., Choutko, A., Riniker, S., Winger, M., Mark, A. E., and Van Gunsteren, W. F. (2011) Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur. Biophys. J. 40, 843-856
66. Brown, N. P., Leroy, C., and Sander, C. (1998) MView: a web-compatible database search or multiple alignment viewer. Bioinformatics 14, 380-381
67. Guo, Z., Kraka, E., and Cremer, D. (2013) Description of local and global shape properties of protein helices. J. Mol. Model. 19, 2901-2911
68. El Hiani, Y., and Linsdell, P. (2010) Changes in accessibility of cytoplasmic substances to the pore associated with activation of the cystic fibrosis transmembrane conductance regulator chloride channel. J. Biol. Chem. 285, 32126-32140
69. Qian, F., El Hiani, Y., and Linsdell, P. (2011) Functional arrangement of the 12th transmembrane region in the CFTR chloride channel pore based on functional investigation of a cysteine-less CFTR variant. Pflugers Arch. 462, 559-571
70. Wang, W., El Hiani, Y., Rubaiy, H. N., and Linsdell, P. (2014) Relative contribution of different transmembrane segments to the CFTR chloride channel pore. Pflugers Arch. 466, 477-490
71. Wang, W., El Hiani, Y., and Linsdell, P. (2011) Alignment of transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore. J. Gen. Physiol. 138, 165-178
72. Bai, Y., Li, M., and Hwang, T. C. (2010) Dual roles of the sixth transmembrane segment of the CFTR chloride channel in gating and permeation. J. Gen. Physiol. 136, 293-309
73. Bai, Y., Li, M., and Hwang, T. C. (2011) Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7). J. Gen. Physiol. 138, 495-507
74. Gao, X., Bai, Y., and Hwang, T. C. (2013) Cysteine scanning of CFTR's first transmembrane segment reveals its plausible roles in gating and permeation. Biophys. J. 104, 786-797
75. Anderson, M. P., Gregory, R. J., Thompson, S., Souza, D. W., Paul, S., Mulligan, R. C, Smith, A. E., and Welsh, M. J. (1991) Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 253, 202-205
76. - channels with altered pore properties. Nature 362, 160-164
77. Gong, X., and Linsdell, P. (2003) Mutation-induced blocker permeability and multi-ion block of the CFTR chloride channel pore. J. Gen. Physiol. 122, 673-687
78. Zhou, J. J., Fatehi, M., and Linsdell, P. (2008) Identification of positive charges situated at the outer mouth of the CFTR chloride channel pore. Pflugers Arch. 457, 351-360
79. Linsdell, P. (2001) Relationship between anion binding and anion permeability revealed by mutagenesis within the cystic fibrosis transmembrane conductance regulator chloride channel pore. J. Physiol. 531, 51-66
80. Linsdell, P., Evagelidis, A., and Hanrahan, J. W. (2000) Molecular determinants of anion selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel pore. Biophys. J. 78, 2973-2982
81. McCarty, N. A., and Zhang, Z. R. (2001) Identification of a region of strong discrimination in the pore of CFTR. Am. J. Physiol. Lung Cell. Mol. Physiol. 281, L852-L867
82. Férec, C, Verlingue, C, Guillermit, H., Quéré, I., Raguénès, O., Feigelson, J., Audrézet, M. P., Moullier, P., and Mercier, B. (1993) Genotype analysis of adult cystic fibrosis patients. Hum. Mol. Genet. 2, 1557-1560
83. Schaedel, C, Andersson, A. M., Kristoffersson, A. C, Kornfält, R., Lannefors, L., and Holmberg, L. (1998) Mild cystic fibrosis mutations in Southern Sweden with special reference to S549I and T338I. Clin. Genet. 53, 383-386
84. Beckstein, O., and Sansom, M. S. (2006) A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor. Phys. Biol. 3, 147-159
85. Gao, X., and Hwang, T. C. (2015) Localizing a gate in CFTR. Proc. Natl. Acad. Sci. U. S. A. 112, 2461-2466
86. Zhu, F., and Hummer, G. (2010) Pore opening and closing of a pentameric ligand-gated ion channel. Proc. Natl. Acad. Sci. U. S. A. 107, 19814-19819
87. Smith, S. S., Steinle, E. D., Meyerhoff, M. E., and Dawson, D. C. (1999) Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns. J. Gen. Physiol. 114, 799-818
88. Linsdell, P., and Hanrahan, J. W. (1998) Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. J. Gen. Physiol. 111, 601-614
89. Linsdell, P., Tabcharani, J. A., Rommens, J. M., Hou, Y. X., Chang, X. B., Tsui, L. C, Riordan, J. R., and Hanrahan, J. W. (1997) Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions. J. Gen. Physiol. 110, 355-364
90. Wang, X., Bompadre, S. G., Li, M., and Hwang, T. C. (2009) Mutations at the signature sequence of CFTR create a Cd2+-gated chloride channel. J. Gen. Physiol. 133, 69-77
91. Wang, W., Bernard, K., Li, G., and Kirk, K. L. (2007) Curcumin opens cystic fibrosis transmembrane conductance regulator channels by a novel mechanism that requires neither ATP binding nor dimerization of the nucleotide-binding domains. J. Biol. Chem. 282, 4533-4544
92. Chen, H. L., Gabrilovich, D., Tampé, R., Girgis, K. R., Nadaf, S., and Carbone, D. P. (1996) A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nat. Genet. 13, 210-213
93. Conseil, G., Rothnie, A. J., Deeley, R. G., and Cole, S. P. (2009) Multiple roles of charged amino acids in cytoplasmic loop 7 for expression and function of the multidrug and organic anion transporter MRP1 (ABCC1). Mol. Pharmacol. 75, 397-406
94. Fülöp, K., Barna, L., Symmons, O., Závodszky, P., and Váradi, A. (2009) Clustering of disease-causing mutations on the domain-domain interfaces of ABCC6. Biochem. Biophys. Res. Commun. 379, 706-709
95. Oancea, G., O'Mara, M. L., Bennett, W. F., Tieleman, D. P., Abele, R., and Tampé, R. (2009) Structural arrangement of the transmission interface in the antigen ABC transport complex TAP. Proc. Natl. Acad. Sci. U. S. A. 106, 5551-5556
96. Weng, J. W., Fan, K. N., and Wang, W. N. (2010) The conformational transition pathway of ATP-binding cassette transporter MsbA revealed by atomistic simulations. J. Biol. Chem. 285, 3053-3063
97. Damas, J. M., Oliveira, A. S., Baptista, A. M., and Soares, C. M. (2011) Structural consequences of ATP hydrolysis on the ABC transporter NBD dimer: molecular dynamics studies of HlyB. Protein Sci. 20, 1220-1230
98. Aittoniemi, J., De Wet, H, Ashcroft, F. M., and Sansom, M. S. (2010) Asymmetric switching in a homodimeric ABC transporter: a simulation study. PLoS Comput. Biol. 6, e1000762
99. Becker, J. P., Van Bambeke, F., Tulkens, P. M., and Prévost, M. (2010) Dynamics and structural changes induced by ATP binding in SAV1866, a bacterial ABC exporter. J. Phys. Chem. B. 114, 15948-15957
100. He, L., Aleksandrov, A. A., Serohijos, A. W., Hegedus, T., Aleksandrov, L. A., Cui, L., Dokholyan, N. V., and Riordan, J. R. (2008) Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate regulation of channel gating. J. Biol. Chem. 283, 26383-26390
101. Wang, W., and Linsdell, P. (2012) Alternating access to the transmembrane domain of the ATP-binding cassette protein cystic fibrosis transmembrane conductance regulator (ABCC7). J. Biol. Chem. 287, 10156-10165
102. Aubin, C. N., and Linsdell, P. (2006) Positive charges at the intracellular mouth of the pore regulate anion conduction in the CFTR chloride channel. J. Gen. Physiol. 128, 535-545
103. El Hiani, Y., and Linsdell, P. (2015) Functional architecture of the cytoplasmic entrance to the cystic fibrosis transmembrane conductance regulator chloride channel pore. J. Biol. Chem. 290, 15855-15865
104. Linsdell, P. (2005) Location of a common inhibitor binding site in the cytoplasmic vestibule of the cystic fibrosis transmembrane conductance regulator chloride channel pore. J. Biol. Chem. 280, 8945-8950
105. Csanády, L., and Töröcsik, B. (2014) Catalyst-like modulation of transition states for CFTR channel opening and closing: new stimulation strategy exploits nonequilibrium gating. J. Gen. Physiol. 143, 269-287
106. Sebastian, A., Rishishwar, L., Wang, J., Bernard, K. F., Conley, A. B., McCarty, N. A., and Jordan, I. K. (2013) Origin and evolution of the cystic fibrosis transmembrane regulator protein R domain. Gene 523, 137-146
107. Ritz, U., Drexler, I., Sutter, D., Abele, R., Huber, C, and Seliger, B. (2003) Impaired transporter associated with antigen processing (TAP) function attributable to a single amino acid alteration in the peptide TAP subunit TAP1. J. Immunol. 170, 941-946
108. Linsdell, P. (2014) Functional architecture of the CFTR chloride channel. Mol. Membr. Biol. 31, 1-16
109. Wang, W., Roessler, B. C., and Kirk, K. L. (2014) An electrostatic interaction at the tetrahelix bundle promotes phosphorylation-dependent cystic fibrosis transmembrane conductance regulator (CFTR) channel opening. J. Biol. Chem. 289, 30364-30378
110. Wang, W., and Linsdell, P. (2012) Conformational change opening the CFTR chloride channel pore coupled to ATP-dependent gating. Biochim. Biophys. Acta 1818, 851-860
111. El Hiani, Y., and Linsdell, P. (2014) Metal bridges illuminate transmembrane domain movements during gating of the cystic fibrosis transmembrane conductance regulator chloride channel. J. Biol. Chem. 289, 28149-28159
112. El Hiani, Y., and Linsdell, P. (2014) Conformational changes opening and closing the CFTR chloride channel: insights from cysteine scanning mutagenesis. Biochem. Cell Biol. 92, 481-488
113. Gadsby, D. C. (2009) Ion channels versus ion pumps: the principal difference, in principle. Nat. Rev. Mol. Cell Biol. 10, 344-352
114. Wang, G. (2015) Molecular basis for Fe (III)-independent curcumin potentiation of cystic fibrosis transmembrane conductance regulator activity. Biochemistry 54, 2828-2840