Insights into the mechanisms underlying CFTR channel activity, the molecular basis for cystic fibrosis and strategies for therapy

Essays in Biochemistry

Volumn 50, Issue 1, 2011, Pages 233-248

  Chiaw, Patrick Kim ^a   Eckford, Paul D W ^a   Bear, Christine E ^a  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

PROKARYOTA;

TRANSMEMBRANE CONDUCTANCE REGULATOR;

CHANNEL GATING; CHEMICAL STRUCTURE; CHEMISTRY; CYSTIC FIBROSIS; GENETICS; HUMAN; METABOLISM; MUTATION; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN CONFORMATION; REVIEW;

CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMANS; ION CHANNEL GATING; MODELS, MOLECULAR; MUTATION; PHOSPHORYLATION; PROTEIN CONFORMATION;

EID: 79953183131     PISSN: 00711365     EISSN: None     Source Type: Journal    
DOI: 10.1042/BSE0500233     Document Type: Article

References (67)

1. Rowe, S.M., Miller, S. and Sorscher, E.J. (2005) Cystic fibrosis. N. Engl. J. Med. 352, 1992-2001
2. Boucher, R.C. (2007) Cystic fibrosis: a disease of vulnerability to airway surface dehydration. Trends Mol. Med. 13, 231-240
3. Dawson, R.J., Hollenstein, K. and Locher, K.P. (2007) Uptake or extrusion: crystal structures of full ABC transporters suggest a common mechanism. Mol. Microbiol. 65, 250-257
4. Bear, C.E., Li, C.H., Kartner, N., Bridges, R.J., Jensen, T.J., Ramjeesingh, M. and Riordan, J.R. (1992) Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell 68, 809-818
5. Accardi, A. and Picollo, A. (2010) CLC channels and transporters: proteins with borderline personalities. Biochim. Biophys. Acta 1798, 1457-1464
6. Lewis, H.A., Zhao, X., Wang, C., Sauder, J.M., Rooney, I., Noland, B.W., Lorimer, D., Kearins, M.C., Conners, K., Condon, B. et al. (2005) Impact of the ΔF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J. Biol. Chem. 280, 1346-1353
7. 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. et al. (2004) Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. EMBO J. 23, 282-293
8. Rosenberg, M.F., Kamis, A.B., Aleksandrov, L.A., Ford, R.C. and Riordan, J.R. (2004) Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR). J. Biol. Chem. 279, 39051-39057
9. Zhang, L., Aleksandrov, L.A., Zhao, Z., Birtley, J.R., Riordan, J.R. and Ford, R.C. (2009) Architecture of the cystic fibrosis transmembrane conductance regulator protein and structural changes associated with phosphorylation and nucleotide binding. J. Struct. Biol. 167, 242-251
10. Awayn, N.H., Rosenberg, M.F., Kamis, A.B., Aleksandrov, L.A., Riordan, J.R. and Ford, R.C. (2005) Crystallographic and single-particle analyses of native- and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Biochem. Soc. Trans. 33, 996-999
11. 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
12. 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
13. 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
14. Dawson, R.J. and Locher, K.P. (2006) Structure of a bacterial multidrug ABC transporter. Nature 443, 180-185
15. 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
16. Karpowich, N., Martsinkevich, O., Millen, L., Yuan, Y.R., Dai, P.L., MacVey, K., Thomas, P.J. and Hunt, J.F. (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, 571-586
17. Atwell, S., Brouillette, C.G., Conners, K., Emtage, S., Gheyi, T., Guggino, W.B., Hendle, J., Hunt, J.F., Lewis, H.A., Lu, F. 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
18. Gadsby, D.C., Vergani, P. and Csanady, L. (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477-483
19. - channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol. 587, 2151-2161
20. Ramjeesingh, M., Ugwu, F., Stratford, F.L., Huan, L.J., Li, C. and Bear, C.E. (2008) The intact CFTR protein mediates ATPase rather than adenylate kinase activity. Biochem. J. 412, 315-321
21. Beaudet, L. and Gros, P. (1998) Mutational analysis of P-glycoprotein in yeast Saccharomyces cerevisiae. Methods Enzymol. 292, 414-427
22. Zeltwanger, S., Wang, F., Wang, G.T., Gillis, K.D. and Hwang, T.C. (1999) Gating of cystic fibrosis transmembrane conductance regulator chloride channels by adenosine triphosphate hydrolysis: quantitative analysis of a cyclic gating scheme. J. Gen. Physiol. 113, 541-554
23. Aleksandrov, A.A., Cui, L. and Riordan, J.R. (2009) Relationship between nucleotide binding and ion channel gating in cystic fibrosis transmembrane conductance regulator. J. Physiol. 587, 2875-2886
24. - ion pore revealed by distributions of open channel burst durations. Proc. Natl. Acad. Sci. U.S.A. 107, 1241-1246
25. Muallem, D. and Vergani, P. (2009) ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator. Philos. Trans. R. Soc. London Ser. B 364, 247-255
26. Chakrabarti, N., Neale, C., Payandeh, J., Pai, E.F. and Pomes, R. (2010) An iris-like mechanism of pore dilation in the CorA magnesium transport system. Biophys. J. 98, 784-792
27. Wang, W., Wu, J., Bernard, K., Li, G., Wang, G., Bevensee, M.O. and Kirk, K.L. (2010) ATP-independent CFTR channel gating and allosteric modulation by phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 107, 3888-3893
28. Linsdell, P. (2006) Mechanism of chloride permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. Exp. Physiol. 91, 123-129
29. Sheppard, D.N. and Welsh, M.J. (1999) Structure and function of the CFTR chloride channel. Physiol. Rev. 79, S23-S45
30. McCarty, N.A. (2000) Permeation through the CFTR chloride channel. J. Exp. Biol. 203, 1947-1962
31. 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
32. Zhou, J.J., Li, M.S., Qi, J. and 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
33. 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
34. Fatehi, M. and Linsdell, P. (2008) State-dependent access of anions to the cystic fibrosis transmembrane conductance regulator chloride channel pore. J. Biol. Chem. 283, 6102-6109
35. 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
36. Cheng, S.H., Rich, D.P., Marshall, J., Gregory, R.J., Welsh, M.J. and Smith, A.E. (1991) Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. Cell 66, 1027-1036
37. - secretion by AMPK in vivo. Pflügers Arch. 457, 1071-1078
38. - channel in CHO cells stably expressing the cystic fibrosis gene. Nature 352, 628-631
39. Chappe, V., Irvine, T., Liao, J., Evagelidis, A. and Hanrahan, J.W. (2005) Phosphorylation of CFTR by PKA promotes binding of the regulatory domain. EMBO J. 24, 2730-2740
40. Ostedgaard, L.S., Baldursson, O., Vermeer, D.W., Welsh, M.J. and Robertson, A.D. (2000) A functional R domain from cystic fibrosis transmembrane conductance regulator is predominantly unstructured in solution. Proc. Natl. Acad. Sci. U.S.A. 97, 5657-5662
41. Baker, J.M., Hudson, R.P., Kanelis, V., Choy, W.Y., Thibodeau, P.H., Thomas, P.J. and Forman-Kay, J.D. (2007) CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices. Nat. Struct. Mol. Biol. 14, 738-745
42. Hegedus, T., Serohijos, A.W., Dokholyan, N.V., He, L. and Riordan, J.R. (2008) Computational studies reveal phosphorylation-dependent changes in the unstructured R domain of CFTR. J. Mol. Biol. 378, 1052-1063
43. Mense, M., Vergani, P., White, D.M., Altberg, G., Nairn, A.C. and Gadsby, D.C. (2006) In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer. EMBO J. 25, 4728-4739
44. Naren, A.P., Cormet-Boyaka, E., Fu, J., Villain, M., Blalock, J.E., Quick, M.W. and Kirk, K.L. (1999) CFTR chloride channel regulation by an interdomain interaction. Science 286, 544-548
45. Seibert, F.S., Chang, X.B., Aleksandrov, A.A., Clarke, D.M., Hanrahan, J.W. and Riordan, J.R. (1999) Influence of phosphorylation by protein kinase A on CFTR at the cell surface and endoplasmic reticulum. Biochim. Biophys. Acta 1461, 275-283
46. Chang, X.B., Tabcharani, J.A., Hou, Y.X., Jensen, T.J., Kartner, N., Alon, N., Hanrahan, J.W. and Riordan, J.R. (1993) Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all 10 PKA consensus phosphorylation sites. J. Biol. Chem. 268, 11304-11311
47. Gadsby, D.C. and Nairn, A.C. (1999) Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis. Physiol. Rev. 79, S77-S107
48. Li, C., Ramjeesingh, M., Wang, W., Garami, E., Hewryk, M., Lee, D., Rommens, J.M., Galley, K. and Bear, C.E. (1996) ATPase activity of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 271, 28463-28468
49. Wilkinson, D.J., Strong, T.V., Mansoura, M.K., Wood, D.L., Smith, S.S., Collins, F.S. and Dawson, D.C. (1997) CFTR activation: additive effects of stimulatory and inhibitory phosphorylation sites in the R domain. Am. J. Physiol. 273, L127-L133
50. Kerem, B., Rommens, J.M., Buchanan, J.A., Markiewicz, D., Cox, T.K., Chakravarti, A., Buchwald, M. and Tsui, L.C. (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080
51. 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
52. Younger, J.M., Chen, L., Ren, H.Y., Rosser, M.F., Turnbull, E.L., Fan, C.Y., Patterson, C. and Cyr, D.M. (2006) Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell 126, 571-582
53. Pissarra, L.S., Farinha, C.M., Xu, Z., Schmidt, A., Thibodeau, P.H., Cai, Z., Thomas, P.J., Sheppard, D.N. and Amaral, M.D. (2008) Solubilizing mutations used to crystallize one CFTR domain attenuate the trafficking and channel defects caused by the major cystic fibrosis mutation. Chem. Biol. 15, 62-69
54. Chen, E.Y., Bartlett, M.C., Loo, T.W. and Clarke, D.M. (2004) The ΔF508 mutation disrupts packing of the transmembrane segments of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 279, 39620-39627
55. Du, K., Sharma, M. and Lukacs, G.L. (2005) The ΔF508 cystic fibrosis mutation impairs domain- domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 12, 17-25
56. Wang, X., Matteson, J., An, Y., Moyer, B., Yoo, J.S., Bannykh, S., Wilson, I.A., Riordan, J.R. and Balch, W.E. (2004) COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. J. Cell Biol. 167, 65-74
57. Chang, X.B., Cui, L., Hou, Y.X., Jensen, T.J., Aleksandrov, A.A., Mengos, A. and Riordan, J.R. (1999) Removal of multiple arginine-framed trafficking signals overcomes misprocessing of ΔF508 CFTR present in most patients with cystic fibrosis. Mol. Cell 4, 137-142
58. Teem, J.L., Berger, H.A., Ostedgaard, L.S., Rich, D.P., Tsui, L.C. and Welsh, M.J. (1993) Identification of revertants for the cystic fibrosis ΔF508 mutation using STE6-CFTR chimeras in yeast. Cell 73, 335-346
59. Kim Chiaw, P., Huan, L.J., Gagnon, S., Ly, D., Sweezey, N., Rotin, D., Deber, C.M. and Bear, C.E. (2009) Functional rescue of ΔF508-CFTR by peptides designed to mimic sorting motifs. Chem. Biol. 16, 520-530
60. Denning, G.M., Anderson, M.P., Amara, J.F., Marshall, J., Smith, A.E. and Welsh, M.J. (1992) Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 358, 761-764
61. Robert, R., Carlile, G.W., Liao, J., Balghi, H., Lesimple, P., Liu, N., Kus, B., Rotin, D., Wilke, M., de Jonge, H.R. et al. (2010) Correction of the ΔPhe508 cystic fibrosis transmembrane conductance regulator trafficking defect by the bioavailable compound glafenine. Mol. Pharmacol. 77, 922-930
62. Van Goor, F., Straley, K.S., Cao, D., Gonzalez, J., Hadida, S., Hazlewood, A., Joubran, J., Knapp, T., Makings, L.R., Miller, M. et al. (2006) Rescue of ΔF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L1117-L1130
63. Pedemonte, N., Lukacs, G.L., Du, K., Caci, E., Zegarra-Moran, O., Galietta, L.J. and Verkman, A.S. (2005) Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest. 115, 2564-2571
64. Wang, Y., Loo, T.W., Bartlett, M.C. and Clarke, D.M. (2007) Correctors promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein. J. Biol. Chem. 282, 33247-33251
65. Kim Chiaw, P., Wellhauser, L., Huan, L.J., Ramjeesingh, M. and Bear, C. (2010) A chemical corrector modifies the channel function of F508del-CFTR. Mol. Pharmacol. 78, 411-418
66. Van Goor, F., Hadida, S., Grootenhuis, P.D., Burton, B., Cao, D., Neuberger, T., Turnbull, A., Singh, A., Joubran, J., Hazlewood, A. et al. (2009) Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc. Natl. Acad. Sci. U.S.A. 106, 18825-18830
67. Wellhauser, L., Kim Chiaw, P., Pasyk, S., Li, C., Ramjeesingh, M. and Bear, C.E. (2009) A small-molecule modulator interacts directly with ΔPhe508-CFTR to modify its ATPase activity and conformational stability. Mol. Pharmacol. 75, 1430-1438