Architecture and functional properties of the CFTR channel pore

Cellular and Molecular Life Sciences

Volumn 74, Issue 1, 2017, Pages 67-83

  Linsdell, Paul ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

ABC protein; CFTR; Channel pore; Chloride channel; Cystic fibrosis; Ion selectivity

Indexed keywords

ANION; CHLORIDE ION; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR;

BINDING AFFINITY; BIOPHYSICS; CHANNEL GATING; CHLORIDE TRANSPORT; CYTOPLASM; ELECTROPHYSIOLOGY; ENZYME PHOSPHORYLATION; GENE MUTATION; HUMAN; ION CONDUCTANCE; MEMBRANE PERMEABILITY; MOLECULAR DYNAMICS; MOLECULAR MODEL; PARTICLE SIZE; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CELL MEMBRANE; CHEMISTRY; CYSTIC FIBROSIS; METABOLISM; PROTEIN CONFORMATION;

ANIMALS; ANIONS; CELL MEMBRANE; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; CYTOPLASM; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION;

EID: 84989905185     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-016-2389-5     Document Type: Review

References (105)

1. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou J-L, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073
2. Dean M, Rzhetsky A, Alikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156–1166
3. Rees DC, Johnson E, Lewinson O (2009) ABC transporters: the power to change. Nat Rev Mol Cell Biol 10:218–227
4. ter Beek J, Guskov A, Slotboom DJ (2014) Structural diversity of ABC transporters. J Gen Physiol 143:419–435
5. Gadsby DC, Vergani P, Csanády L (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440:477–483
6. A receptor. Nature 512:270–275
7. Du J, Lü W, Wu S, Cheng Y, Gouaux E (2015) Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526:224–229
8. Huang X, Chen H, Michelsen K, Schneider S, Shaffer PL (2015) Crystal structure of human glycine receptor-α3 bound to antagonist strychnine. Nature 526:277–280
9. Accardi A (2015) Structure and gating of CLC channels and exchangers. J Physiol 593:4129–4138
10. Pedemonte N, Galietta LJV (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459
11. − channel. Nature 516:213–218
12. Jentsch TJ, Lutter D, Planells-Cases R, Ullrich F, Voss FK (2016) VRAC: molecular identification as LRRC8 heteromers with differential functions. Pflügers Arch 468:385–393
13. Frizzell RA, Hanrahan JW (2012) Physiology of epithelial chloride and fluid secretion. Cold Spring Harb Perspect Med 2:a009563
14. Jih K-Y, Hwang T-C (2012) Nonequilibrium gating of CFTR on an equilibrium theme. Physiology 27:351–361
15. Chong PA, Kota P, Dokholyan NV, Forman-Kay JD (2013) Dynamics intrinsic to cystic fibrosis transmembrane conductance regulator function and stability. Cold Spring Harb Perspect Med 3:a009522
16. Hwang T-C, Kirk KL (2013) The CFTR ion channel: gating, regulation, and anion permeation. Cold Spring Harb Perspect Med 3:a009498
17. Linsdell P, Hanrahan JW (1998) Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. J Gen Physiol 111:601–614
18. McCarty NA, Zhang Z-R (2001) Identification of a region of strong discrimination in the pore of CFTR. Am J Physiol 281:L852–L867
19. Tabcharani JA, Linsdell P, Hanrahan JW (1997) Halide permeation in wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels. J Gen Physiol 110:341–354
20. Smith SS, Steinle ED, Meyerhoff ME, Dawson DC (1999) Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns. J Gen Physiol 114:799–818
21. Linsdell P, Evagelidis A, Hanrahan JW (2000) Molecular determinants of anion selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel pore. Biophys J 78:2973–2982
22. Linsdell P (2014) Functional architecture of the CFTR chloride channel. Mol Membr Biol 31:1–16
23. Linsdell P (2016) Anion conductance selectivity mechanism of the CFTR chloride channel. Biochim Biophys Acta 1858:740–747
24. 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
25. Linsdell P (2014) Cystic fibrosis transmembrane conductance regulator chloride channel blockers: pharmacological, biophysical and physiological relevance. World J Biol Chem 5:26–39
26. Rubaiy HN, Linsdell P (2015) Location of a permeant anion binding site in the cystic fibrosis transmembrane conductance regulator chloride channel pore. J Physiol Sci 65:233–241
27. Linsdell P (2015) Interactions between permeant and blocking anions inside the CFTR chloride channel pore. Biochim Biophys Acta 1848:1573–1590
28. Muanprasat C, Sonawane ND, Salinas D, Taddei A, Galietta LJV, Verkman AS (2004) Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J Gen Physiol 124:125–137
29. Zhou J-J, Fatehi M, Linsdell P (2007) Direct and indirect effects of mutations at the outer mouth of the CFTR chloride channel pore. J Membr Biol 216:129–142
30. Zhou J-J, Fatehi M, Linsdell P (2008) Identification of positive charges situated at the outer mouth of the CFTR chloride channel pore. Pflügers Arch 457:351–360
31. Bormann J, Hamill OP, Sakmann B (1987) Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones. J Physiol 385:243–286
32. Fahlke C (2001) Ion permeation and selectivity in ClC-type chloride channels. Am J Physiol 280:F748–F757
33. Machaca K, Qu Z, Kuruma A, Hartzell HC, McCarty NA (2002) The endogenous calcium-activated Cl channel in Xenopus oocytes: a physiologically and biophysically rich model system. Curr Top Membr 53:3–39
34. Hartzell C, Putzier I, Arreola J (2005) Calcium-activated chloride channels. Annu Rev Physiol 67:719–758
35. Linsdell P (2006) Mechanism of chloride permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. Exp Physiol 91:123–129
36. Reyes JP, López-Rodríguez A, Espino-Saldaña AE, Huanosta-Gutiérrez A, Miledi R, Martínez-Torres A (2014) Anion permeation in calcium-activated chloride channels formed by TMEM16A from Xenopus tropicalis. Pflügers Arch 466:1769–1777
37. Rosenberg MF, O’Ryan LP, Hughes G, Zhao Z, Aleksandrov LA, Riordan JR, Ford RC (2011) The cystic fibrosis transmembrane conductance regulator (CFTR). Three-dimensional structure and localization of a channel gate. J Biol Chem 286:42647–42654
38. Hunt JF, Wang C, Ford RC (2013) Cystic fibrosis transmembrane conductance regulator (ABCC7) structure. Cold Spring Harb Perspect Med 3:a009514
39. Choudhury HG, Tong Z, Mathavan I, Li Y, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis K (2014) Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc Natl Acad Sci USA 111:9145–9150
40. Lee JY, Yang JG, Zhitnitsky D, Lewinson O, Rees DC (2014) Structural basis for heavy metal detoxification by an Atm1-type ABC exporter. Science 343:1133–1136
41. Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB, Stiller SB, Robles-Colmanares Y, Stroud RM, Tampé R, Craik CS, Cheng Y (2015) Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature 517:396–400
42. Mornon J-P, Hoffmann B, Jonic S, Lehn P, 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
43. Corradi V, Vergani P, Tieleman DP (2015) Cystic fibrosis transmembrane conductance regulator (CFTR): closed and open state channel models. J Biol Chem 290:22891–22906
44. − channels expressed in a mammalian cell line and its regulation by a critical pore residue. J Physiol 496:687–693
45. − channels expressed in a murine cell line. J Physiol 503:333–346
46. 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
47. El Hiani Y, 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
48. El Hiani Y, Negoda A, Linsdell P (2016) Cytoplasmic pathway followed by chloride ions to enter the CFTR channel pore. Cell Mol Life Sci 73:1917–1925
49. El Hiani Y, Linsdell P (2014) Conformational changes opening and closing the CFTR chloride channel: insights from cysteine scanning mutagenesis. Biochem Cell Biol 92:481–488
50. El Hiani Y, 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
51. Linsdell P (2014) State-dependent blocker interactions with the CFTR chloride channel: implications for gating the pore. Pflügers Arch 466:2243–2255
52. Bai Y, Li M, 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
53. El Hiani Y, 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
54. Bai Y, Li M, Hwang T-C (2011) Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7). J Gen Physiol 138:495–507
55. Qian F, El Hiani Y, Linsdell P (2011) Functional arrangement of the 12th transmembrane region in the CFTR chloride channel based on functional investigation of a cysteine-less variant. Pflügers Arch 462:559–571
56. Wang W, El Hiani Y, Linsdell P (2011) Alignment of transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore. J Gen Physiol 138:165–178
57. Gao X, Bai Y, 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
58. Fatehi M, Linsdell P (2009) Novel residues lining the CFTR chloride channel pore identified by functional modification of introduced cysteines. J Membr Biol 228:151–164
59. Wang W, El Hiani Y, Rubaiy HN, Linsdell P (2014) Relative contribution of different transmembrane segments to the CFTR chloride channel pore. Pflügers Arch 466:477–490
60. Zhang J, Hwang T-C (2015) The fifth transmembrane segment of cystic fibrosis transmembrane conductance regulator contributes to its anion permeation pathway. Biochemistry 54:3839–3850
61. Gupta J, Evagelidis A, Hanrahan JW, Linsdell P (2001) Asymmetric structure of the cystic fibrosis transmembrane conductance regulator chloride channel pore suggested by mutagenesis of the twelfth transmembrane region. Biochemistry 40:6620–6627
62. Ge N, Muise CN, Gong X, Linsdell P (2004) Direct comparison of the functional roles played by different transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore. J Biol Chem 279:55283–55289
63. Zhou J-J, Li M-S, Qi J, Linsdell P (2010) Regulation of conductance by the number of fixed positive charges in the intracellular vestibule of the CFTR chloride channel pore. J Gen Physiol 135:229–245
64. St Aubin CN, 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
65. Smith SS, Liu X, Zhang Z-R, Sun F, Kriewall TE, McCarty NA, Dawson DC (2001) CFTR: covalent and noncovalent modification suggests a role for fixed charges in anion conduction. J Gen Physiol 118:407–431
66. Broadbent SD, Wang W, Linsdell P (2014) Interaction between two extracellular loops influences the activity of the cystic fibrosis transmembrane conductance regulator chloride channel. Biochem Cell Biol 92:390–396
67. Cui G, Rahman KS, Infield DT, Kuang C, Prince CZ, McCarty NA (2014) Three charged amino acids in extracellular loop 1 are involved in maintaining the outer pore architecture of CFTR. J Gen Physiol 144:159–179
68. Hämmerle MM, Aleksandrov AA, Riordan JR (2001) Disease-associated mutations in the extracytoplasmic loops of cystic fibrosis transmembrane conductance regulator do not impede biosynthetic processing but impair chloride channel stability. J Biol Chem 276:14848–14854
69. Infield DT, Cui G, Kuang C, McCarty NA (2016) Positioning of extracellular loop 1 affects pore gating of the cystic fibrosis transmembrane conductance regulator. Am J Physiol 310:L403–L414
70. Li M-S, Cowley EA, Linsdell P (2012) Pseudohalide anions reveal a novel extracellular site for potentiators to increase CFTR function. Br J Pharmacol 167:1062–1075
71. Broadbent SD, Ramjeesingh M, Bear CE, Argent BE, Linsdell P, Gray MA (2015) The cystic fibrosis transmembrane conductance regulator is an extracellular chloride sensor. Pflügers Arch 467:1783–1794
72. Wright AM, Gong X, Verdon B, Linsdell P, Mehta A, Riordan JR, Argent BE, Gray MA (2004) Novel regulation of CFTR channel gating by external chloride. J Biol Chem 279:41658–41663
73. Li M-S, Holstead RG, Wang W, Linsdell P (2011) Regulation of CFTR chloride channel macroscopic conductance by extracellular bicarbonate. Am J Physiol 300:C65–C74
74. Zhou J-J, Linsdell P (2009) Evidence that extracellular anions interact with a site outside the CFTR chloride channel pore to modify channel properties. Can J Physiol Pharmacol 87:387–395
75. Beck EJ, Yang Y, Yaemsiri S, Raghuram V (2008) Conformational changes in a pore-lining helix coupled to cystic fibrosis transmembrane conductance regulator channel gating. J Biol Chem 283:4957–4966
76. Gong X, Linsdell P (2004) Maximization of the rate of chloride conduction in the CFTR channel pore by ion-ion interactions. Arch Biochem Biophys 426:78–82
77. Gong X, Linsdell P (2003) Molecular determinants and role of an anion binding site in the external mouth of the CFTR chloride channel pore. J Physiol 549:387–397
78. Rahman KS, Cui G, Harvey SC, McCarty NA (2013) Modeling the conformational changes underlying channel opening in CFTR. PLoS One 8:e74574
79. Wang W, Linsdell P (2012) Relative movements of transmembrane regions at the outer mouth of the cystic fibrosis transmembrane conductance regulator channel pore during channel gating. J Biol Chem 287:32136–32146
80. Linsdell P (2015) Metal bridges to probe membrane ion channel structure and function. Biomol Concepts 6:191–203
81. Zhang Z-R, Song B, McCarty NA (2005) State-dependent chemical reactivity of an engineered cysteine reveals conformational changes in the outer vestibule of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 280:41997–42003
82. Wang W, 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
83. Gao X, Hwang T-C (2015) Localizing a gate in CFTR. Proc Natl Acad Sci USA 112:2461–2466
84. Linsdell P, Tabcharani JA, Rommens JM, Hou Y-X, Chang X-B, Tsui L-C, Riordan JR, Hanrahan JW (1997) Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions. J Gen Physiol 110:355–364
85. Hille B (2001) Ion channels of excitable membranes. Sinauer, Sunderland
86. Gouaux E, MacKinnon R (2005) Principles of selective ion transport in channels and pumps. Science 310:1461–1465
87. − channel expressed in mammalian cell lines. J Physiol 512:1–16
88. Gupta J, Linsdell P (2003) Extent of the selectivity filter region in the CFTR chloride channel. Mol Membr Biol 20:45–52
89. McDonough S, Davidson N, Lester HA, McCarty NA (1994) Novel pore-lining residues in CFTR that govern permeation and open-channel block. Neuron 13:623–634
90. Fatehi M, St. Aubin CN, Linsdell P (2007) On the origin of asymmetric interactions between permeant anions and the CFTR chloride channel pore. Biophys J 92:1241–1253
91. El Hiani Y, Linsdell P (2012) Tuning of CFTR chloride channel function by location of positive charges within the pore. Biophys J 103:1719–1726
92. Sheppard DN, Travis SM, Ishihara H, Welsh MJ (1996) Contribution of proline residues in the membrane-spanning domains of cystic fibrosis transmembrane conductance regulator to chloride channel function. J Biol Chem 271:14995–15001
93. Cui G, Song B, Turki HW, McCarty NA (2012) Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers. Pflügers Arch 463:405–418
94. Gao X, Hwang T-C (2016) Spatial positioning of CFTR’s pore-lining residues affirms an asymmetrical contribution of transmembrane segments to the anion permeation pathway. J Gen Physiol 147:407–422
95. Wei S, Roessler BC, Icyuz M, Chauvet S, Tao B, Hartman JL, Kirk KL (2016) Long-range coupling between the extracellular gates and the intracellular ATP binding domains of multidrug resistance protein pumps and cystic fibrosis transmembrane conductance regulator channels. FASEB J 30:1247–1262
96. Sorum B, Czégé D, Csanády L (2015) Timing of CFTR pore opening and structure of its transition state. Cell 163:724–733
97. Cui G, Zhang Z-R, O’Brien AR, Song B, McCarty NA (2008) Mutations at arginine 352 alter the pore architecture of CFTR. J Membr Biol 222:91–106
98. Jordan IK, Kota KC, Cui G, Thompson CH, McCarty NA (2008) Evolutionary and functional divergence between the cystic fibrosis transmembrane conductance regulator and related ATP-binding cassette transporters. Proc Natl Acad Sci USA 105:18865–18870
99. Wang W, Linsdell P (2012) Conformational change opening the CFTR chloride channel pore coupled to ATP-dependent gating. Biochim Biophys Acta 1818:851–860
100. St Aubin CN, Zhou J-J, Linsdell P (2007) Identification of a second blocker binding site at the cytoplasmic mouth of the cystic fibrosis transmembrane conductance regulator chloride channel pore. Mol Pharmacol 71:1360–1368
101. Zhou J-J, Linsdell P (2007) Molecular mechanism of arachidonic acid inhibition of the CFTR chloride channel. Eur J Pharmacol 563:88–91
102. Gong X, Linsdell P (2003) Coupled movement of permeant and blocking ions in the CFTR chloride channel pore. J Physiol 549:375–385
103. Sather WA, McCleskey EW (2003) Permeation and selectivity in calcium channels. Annu Rev Physiol 65:133–159
104. + channels. Annu Rev Biophys Biomol Struct 34:153–171
105. Zhang Z-R, Zeltwanger S, McCarty NA (2000) Direct comparison of NPPB and DPC as probes of CFTR expressed in Xenopus oocytes. J Membr Biol 175:35–52