Conformational changes relevant to channel activity and folding within the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator

Journal of Biological Chemistry

Volumn 287, Issue 34, 2012, Pages 28480-28494

  Hudson, Rhea P ^a   Chong, P Andrew ^a   Protasevich, Irina I ^b   Vernon, Robert ^a   Noy, Efrat ^c   Bihler, Hermann ^d   An, Jian Li ^b   Kalid, Ori ^e,f   Sela Culang, Inbal ^c,e   Mense, Martin ^d   Senderowitz, Hanoch ^c   Brouillette, Christie G ^b   Forman Kay, Julie D ^a  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c BAR ILAN UNIVERSITY   (Israel)

^d Cystic Fibrosis Foundation Therapeutics   (United States)

^e Epix Pharmaceuticals   (United States)

^f Ori Kalid Consulting   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CHANNEL ACTIVITY; CHANNEL GATING; CHANNEL OPEN PROBABILITY; CONFORMATIONAL CHANGE; CONFORMATIONAL EQUILIBRIUM; CONFORMATIONAL FLUCTUATIONS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATORS; DOCKING SIMULATIONS; NMR ASSIGNMENT; NMR DATA; NUCLEOTIDE-BINDING DOMAIN; REGULATORY REGIONS;

DIFFERENTIAL SCANNING CALORIMETRY; DIMERIZATION;

PROTEINS;

GLUTAMINE; HISTIDINE; SERINE; TRANSMEMBRANE CONDUCTANCE REGULATOR;

ALPHA HELIX; ARTICLE; CARBOXY TERMINAL SEQUENCE; CHANNEL GATING; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DIFFERENTIAL SCANNING CALORIMETRY; DIMERIZATION; EQUILIBRIUM CONSTANT; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NUCLEOTIDE BINDING SITE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; THERMOSTABILITY;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMANS; MUTATION, MISSENSE; PROTEIN FOLDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; SEQUENCE DELETION;

EID: 84865234037     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.371138     Document Type: Article

References (69)

1. 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 (Pubitemid 19231815)
2. Rommens, J. M., Iannuzzi, M. C., Kerem, B., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy, D., and Hidaka, N. (1989) Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science 245, 1059-1065 (Pubitemid 19231813)
3. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., and Chou, J. L. (1989) Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245, 1066-1073 (Pubitemid 19231814)
4. 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., Rajashankar, K. R., Rutter, M. E., Sauder, J. M., Shriver, S., Thibodeau, P. H., Thomas, P. J., Zhang, M., Zhao, X., and Emtage, S. (2004) Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. EMBO J. 23, 282-293 (Pubitemid 38294493)
5. Ostedgaard, L. S., Baldursson, O., and Welsh, M. J. (2001) Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by its R domain. J. Biol. Chem. 276, 7689-7692
6. Chappe, V., Hinkson, D. A., Howell, L. D., Evagelidis, A., Liao, J., Chang, X. B., Riordan, J. R., and Hanrahan, J. W. (2004) Stimulatory and inhibitory protein kinase C consensus sequences regulate the cystic fibrosis transmembrane conductance regulator. Proc. Natl. Acad. Sci. U.S.A. 101, 390-395 (Pubitemid 38084260)
7. Hallows, K. R., Raghuram, V., Kemp, B. E., Witters, L. A., and Foskett, J. K. (2000) Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase. J. Clin. Invest. 105, 1711-1721 (Pubitemid 30421752)
8. Smith, P. C., Karpowich, N., Millen, L., Moody, J. E., Rosen, J., Thomas, P. J., and Hunt, J. F. (2002) ATP binding to the motor domain from anABC transporter drives formation of a nucleotide sandwich dimer. Mol. Cell 10, 139-149 (Pubitemid 34876568)
9. 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 (Pubitemid 41170023)
10. 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 (Pubitemid 44607019)
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. Hwang, T. C., and Sheppard, D. N. (2009) Gating of the CFTR Cl- channel by ATP-driven nucleotide-binding domain dimerization. J. Physiol. 587, 2151-2161
13. Bobadilla, J. L., Macek, M., Jr., Fine, J. P., and Farrell, P. M. (2002) Cystic fibrosis: A worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum. Mutat. 19, 575-606 (Pubitemid 34556480)
14. Welsh, M. J., and Smith, A. E. (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73, 1251-1254 (Pubitemid 23201140)
15. 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
16. Sato, S., Ward, C. L., Krouse, M. E., Wine, J. J., and Kopito, R. R. (1996) Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J. Biol. Chem. 271, 635-638 (Pubitemid 26034907)
17. 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 (Pubitemid 23123311)
18. 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
19. Aleksandrov, A. A., Kota, P., Aleksandrov, L. A., He, L., Jensen, T., Cui, L., Gentzsch, M., Dokholyan, N. V., and Riordan, J. R. (2010) Regulatory insertion removal restores maturation, stability and function of ΔF508 CFTR. J. Mol. Biol. 401, 194-210
20. 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 ΔF508 cystic fibrosis mutation. Nature 354, 526-528 (Pubitemid 21896832)
21. Zhang, F., Kartner, N., and Lukacs, G. L. (1998) Limited proteolysis as a probe for arrested conformational maturation of ΔF508 CFTR. Nat. Struct. Biol. 5, 180-183 (Pubitemid 28113747)
22. Van Goor, F., Hadida, S., Grootenhuis, P. D., Burton, B., Stack, J. H., Straley, K. S., Decker, C. J., Miller, M., McCartney, J., Olson, E. R., Wine, J. J., Frizzell, R. A., Ashlock, M., and Negulescu, P. A. (2011) Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc. Natl. Acad. Sci. U.S.A. 108, 18843-18848
23. Clancy, J. P., Rowe, S. M., Accurso, F. J., Aitken, M. L., Amin, R. S., Ashlock, M. A., Ballmann, M., Boyle, M. P., Bronsveld, I., Campbell, P. W., De Boeck, K., Donaldson, S. H., Dorkin, H. L., Dunitz, J. M., Durie, P. R., Jain, M., Leonard, A., McCoy, K. S., Moss, R. B., Pilewski, J. M., Rosenbluth, D. B., Rubenstein, R. C., Schechter, M. S., Botfield, M., Ordoñez, C. L., Spencer-Green, G. T., Vernillet, L., Wisseh, S., Yen, K., and Konstan, M. W. (2012) Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 67, 12-18
24. Accurso, F. J., Rowe, S. M., Clancy, J. P., Boyle, M. P., Dunitz, J. M., Durie, P. R., Sagel, S. D., Hornick, D. B., Konstan, M. W., Donaldson, S. H., Moss, R. B., Pilewski, J. M., Rubenstein, R. C., Uluer, A. Z., Aitken, M. L., Freedman, S. D., Rose, L. M., Mayer-Hamblett, N., Dong, Q., Zha, J., Stone, A. J., Olson, E. R., Ordoñez, C. L., Campbell, P. W., Ashlock, M. A., and Ramsey, B. W. (2010) Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N. Engl. J. Med. 363, 1991-2003
25. Van Goor, F., Hadida, S., Grootenhuis, P. D., Burton, B., Cao, D., Neuberger, T., Turnbull, A., Singh, A., Joubran, J., Hazlewood, A., Zhou, J., McCartney, J., Arumugam, V., Decker, C., Yang, J., Young, C., Olson, E. R., Wine, J. J., Frizzell, R. A., Ashlock, M., and Negulescu, P. (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
26. Van Goor, F., Yu, H., Burton, B., Huang, T., Hoffman, B., and Negulescu, P. A. (2011) VX-770 potentiation of CFTR forms with channel gating defects in vitro. Pediatr. Pulmonol. 34, 215
27. Yu, H., Burton, B., Huang, C. J., Worley, J., Cao, D., Johnson, J. P., Jr., Urrutia, A., Joubran, J., Seepersaud, S., Sussky, K., Hoffman, B. J., and Van Goor, F. (2012) Ivacaftor potentiation of multiple CFTR channels with gating mutations. J. Cyst. Fibros. 11, 237-245
28. Lukacs, G. L., and Verkman, A. S. (2012) CFTR: Folding, misfolding, and correcting the ΔF508 conformational defect. Trends Mol. Med. 18, 81-91
29. Chong, P. A., Kota, P., Dokholyan, N. V., and Forman-Kay, J. D. (2012) Dynamics intrinsic to CFTR function and stability in Cystic Fibrosis: Molecular Basis, Physiological Changes, and Therapeutic Strategies (John Riordan, R. B., and Quinton, P., eds) Cold Spring Harbor Press, Cold Spring Harbor, NY
30. Kanelis, V., Chong, P. A., and Forman-Kay, J. D. (2011) NMR spectroscopy to study the dynamics and interactions of CFTR. Methods Mol. Biol. 741, 377-403
31. Kanelis, V., Hudson, R. P., Thibodeau, P. H., Thomas, P. J., and Forman-Kay, J. D. (2010) NMR evidence for differential phosphorylation-dependent interactions in WT and ΔF508 CFTR. EMBO J. 29, 263-277
32. Protasevich, I., Yang, Z., Wang, C., Atwell, S., Zhao, X., Emtage, S., Wetmore, D., Hunt, J. F., and Brouillette, C. G. (2010) Thermal unfolding studies show the disease causing F508del mutation in CFTR thermodynamically destabilizes nucleotide-binding domain 1. Protein Sci. 19, 1917-1931
33. Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., and Bax, A. (1995) NMRPipe: A multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277-293
34. Johnson, B. A., and Blevins, R. A. (1994) NMR view: A computer program for the visualization and analysis ofNMRdata. J. Biomol.NMR4, 603-614
35. Goddard, T. D., and Kneller, D. G. (2008) Sparky 3, version 3, University of California, San Francisco
36. Yang, D., and Kay, L. E. (1999) Improved 1HN-detected triple resonance TROSY-based experiments. J. Biomol. NMR 13, 3-10 (Pubitemid 29089234)
37. Salzmann, M., Pervushin, K., Wider, G., Senn, H., and Wüthrich, K. (1998) TROSY in triple-resonance experiments: New perspectives for sequential NMR assignment of large proteins. Proc. Natl. Acad. Sci. U.S.A. 95, 13585-13590 (Pubitemid 28523015)
38. Rule, G. S., and Hitchens, T. K. (2006) Fundamentals of Protein NMR Spectroscopy, Springer, Utrecht University, Utrecht, The Netherlands
39. 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 (Pubitemid 41266219)
40. 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 II, Rodgers, L. A., Romero, R., Wasserman, S. R., Weber, P. C., Wetmore, D., Zhang, F. F., and Zhao, X. (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
41. Accelrys (2005-2009) Discovery Studio Modeling Environment, 2.5 Ed., Accelrys Software, Inc., San Diego
42. Berendsen, H. J., van der Spoel, D., and van Drunen, R. (1995) GROMACS: A message-passing parallel molecular dynamics implementation. Comp. Phys. Comm. 91, 43-56
43. Hess, B., Kutzner, C., van der Spoel, D., and Lindahl, E. (2008) GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447
44. Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O., and Shaw, D. E. (2010) Improved side chain torsion potentials for the Amber ff99SB protein force field. Prot. Struct. Funct. Bioinformat. 78, 1950-1958
45. Patriksson, A., and van der Spoel, D. (2008) A temperature predictor for parallel tempering simulations. Phys. Chem. Chem. Phys. 10, 2073-2077
46. Hockney, R. W., Goel, S. P., and Eastwood, J. W. (1974) Quiet high-resolution computer models of a plasma. J. Comput. Phys. 14, 148-158
47. Darden, T., York, D., and Pedersen, L. (1993) Particle mesh Ewald: AnW log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089-10092
48. Essmann, U., Perera, L., Berkowitz, M. L., Darden, T., Lee, H., and Pedersen, L. G. (1995) A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577-8593
49. Hess, B., Bekker, H., Berendsen, H., and Fraaije, J. (1997) LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463-1472 (Pubitemid 127637344)
50. Koska, J., Spassov, V. Z., Maynard, A. J., Yan, L., Austin, N., Flook, P. K., and Venkatachalam, C. M. (2008) Fully automated molecular mechanics based induced fit protein-ligand docking method. J. Chem. Inf. Model. 48, 1965-1973
51. Schrodinger, LLC. (2010) Maestro, version 9.1, Schrodinger, New York
52. Sharma, S., Ding, F., and Dokholyan, N. V. (2007) Multiscale modeling of nucleosome dynamics. Biophys. J. 92, 1457-1470 (Pubitemid 46393459)
53. Schrodinger, LLC (2010) Schrodinger Suite 2010 Induced Fit Docking protocol, Glide, version 5.6, New York, NY
54. Altschul, S. F., Madden, T. L., Schäffer, A. A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D. J. (1997) Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res. 25, 3389-3402 (Pubitemid 27359211)
55. Edgar, R. C. (2004) MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792-1797
56. Billet, A., Melin, P., Jollivet, M., Mornon, J. P., Callebaut, I., and Becq, F. (2010) C terminus of nucleotide binding domain 1 contains critical features for cystic fibrosis transmembrane conductance regulator trafficking and activation. J. Biol. Chem. 285, 22132-22140
57. Wei, L., Vankeerberghen, A., Cuppens, H., Droogmans, G., Cassiman, J. J., and Nilius, B. (1998) Phosphorylation site-independent single R-domain mutations affect CFTR channel activity. FEBS Lett. 439, 121-126 (Pubitemid 28537877)
58. Vankeerberghen, A., Wei, L., Teng, H., Jaspers, M., Cassiman, J. J., Nilius, B., and Cuppens, H. (1998) Characterization of mutations located in exon 18 of the CFTR gene. FEBS Lett. 437, 1-4 (Pubitemid 28498229)
59. Marsh, J. A., Singh, V. K., Jia, Z., and Forman-Kay, J. D. (2006) Sensitivity of secondary structure propensities to sequence differences between α-and γ-synuclein: Implications for fibrillation. Protein Sci. 15, 2795-2804 (Pubitemid 44833760)
60. 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
61. 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 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
62. Sherman, W., Beard, H. S., and Farid, R. (2006) Use of an induced fit receptor structure in virtual screening. Chem. Biol. Drug Des. 67, 83-84 (Pubitemid 43881391)
63. 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 (Pubitemid 47220063)
64. Wang, C., Protasevich, I., Yang, Z., Seehausen, D., Skalak, T., Zhao, X., Atwell, S., Spencer Emtage, J., Wetmore, D. R., Brouillette, C. G., and Hunt, J. F. (2010) Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosis. Protein Sci. 19, 1932-1947
65. Csanády, L., Chan, K. W., Nairn, A. C., and Gadsby, D. C. (2005) Functional roles of nonconserved structural segments in CFTR's NH2-terminal nucleotide binding domain. J. Gen. Physiol. 125, 43-55
66. Seavilleklein, G., Amer, N., Evagelidis, A., Chappe, F., Irvine, T., Hanrahan, J. W., and Chappe, V. (2008) PKC phosphorylation modulates PKA-dependent binding of the R domain to other domains of CFTR. Am. J. Physiol. Cell Physiol. 295, C1366-1375 (Pubitemid 352790322)
67. Wrabl, J. O., Gu, J., Liu, T., Schrank, T. P., Whitten, S. T., and Hilser, V. J. (2011) The role of protein conformational fluctuations in allostery, function, and evolution. Biophys. Chem. 159, 129-141
68. Chang, P., and Ghosh, S. (December 29, 2010) Patent WO 2010/151747 A1
69. Hadida, R. S., Van Goor, F., Miller, M., McCartney, J., and Arumugam, V. (February 22, 2007) Patent WO 2007/021982 A2