Direct interaction of a small-molecule modulator with G551D-CFTR, acystic fibrosis-causing mutation associated with severe disease

Biochemical Journal

Volumn 418, Issue 1, 2009, Pages 185-190

  Pasyk, Stan ^a,b   Li, Canhui ^a   Ramjeesingh, Mohabir ^a   Bear, Christine E ^a,b  

^a HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

ATPase; Chloride channel; Cystic fibrosis (CF); Nucleotide binding domain (NBD); Protein kinase A (PKA); Vesicle flux assay

Indexed keywords

ATPASE; CHLORIDE CHANNEL; CYSTIC FIBROSIS (CF); NUCLEOTIDE-BINDING DOMAIN (NBD); PROTEIN KINASE A (PKA); VESICLE FLUX ASSAY;

CHLORINE COMPOUNDS; MODULATION; NUCLEOTIDES; PROTEINS; PURIFICATION;

MODULATORS;

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATASE; ADENOSINE TRIPHOSPHATE; CHLORIDE CHANNEL; CHLORIDE CHANNEL BLOCKING AGENT; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; VRT 532; CRESOL; GLYCINE; IODIDE; PYRAZOLE DERIVATIVE;

ANIMAL CELL; ARTICLE; BIOCHEMISTRY; CHANNEL GATING; CONTROLLED STUDY; CYSTIC FIBROSIS; DISEASE SEVERITY; DRUG PROTEIN BINDING; ENZYME ACTIVITY; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; HIGH THROUGHPUT SCREENING; MEMBRANE VESICLE; MISSENSE MUTATION; MOUSE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN HYDROLYSIS; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN PURIFICATION; WILD TYPE; ANIMAL; ARMYWORM; CELL LINE; DRUG EFFECT; ENZYME ACTIVATION; GENETICS; KINETICS; METABOLISM; MUTATION; PATHOLOGY;

ADENOSINE TRIPHOSPHATASES; ADENOSINE TRIPHOSPHATE; ANIMALS; CELL LINE; CRESOLS; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; ENZYME ACTIVATION; GLYCINE; IODIDES; KINETICS; MUTATION; PYRAZOLES; SPODOPTERA;

EID: 59849091513     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20081424     Document Type: Article

References (32)

1. Rowe, S. M., Miller, S. and Sorscher, E. J. (2005) Cystic fibrosis. N. Engl. J. Med. 352, 1992-2001
2. 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
3. Riordan, J. R. (2005) Assembly of functional CFTR chloride channels. Annu. Rev. Physiol. 67, 701-718
4. Bompadre, S. G., Sohma, Y., Li, M. and Hwang, T. C. (2007) G551D and G1349D, two CF-associated mutations in the signature sequences of CFTR, exhibit distinct gating defects. J. Gen. Physiol. 129, 285-298
5. Bompadre, S. G., Li, M. and Hwang, T. C. (2008) Mechanism of G551D-CFTR potentiation by a high affinity ATP analog. J. Biol. Chem. 283, 5364-5369
6. Lewis, H. A., Buchanan, S. G., Burley, S. K., Conners, K., Dickey, M., Dorwart, M., Fowler, R., Gao, X., Guggino, W. B. et al. (2004) Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. EMBO J. 23, 282-293
7. 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
8. Hollenstein, K., Frei, D. C. and Locher, K. P. (2007) Structure of an ABC transporter in complex with its binding protein. Nature 446, 213-216
9. Hopfner, K. P., Karcher, A., Shin, D. S., Craig, L., Arthur, L. M., Carney, J. P. and Tainer, J. A. (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
10. 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
11. 2+ transport system. J. Biol. Chem. 283, 11721-11733
12. 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 DeltaF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest. 115, 2564-2571
13. 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 DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L1117-L1130
14. - channel activity in Xenopus oocytes expressing the cystic fibrosis gene. J. Biol. Chem. 266, 19142-19145
15. 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
16. Ramjeesingh, M., Li, C., Garami, E., Huan, L. J., Galley, K., Wang, Y. and Bear, C. E. (1999) Walker mutations reveal loose relationship between catalytic and channel-gating activities of purified CFTR (cystic fibrosis transmembrane conductance regulator). Biochemistry 38, 1463-1468
17. Ramjeesingh, M., Li, C., Kogan, I., Wang, Y., Huan, L. J. and Bear, C. E. (2001) A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator. Biochemistry 40, 10700-10706
18. a Gross, C. H., Abdul-Manan, N., Fulghum, J., Lippke, J., Liu, X., Prabhakar, P., Brennan, D., Willis, M. S., Faerman, C., Connelly, P. et al. (2005) Nucleotide-binding domains of cystic fibrosis transmembrane conductance regulator, an ABC transporter, catalyze adenylate kinase activity but not ATP hydrolysis. J. Biol. Chem. 281, 4058-4068
19. Kartner, N., Hanrahan, J. W., Jensen, T. J., Naismith, A. L., Sun, S. Z., Ackerley, C. A., Reyes, E. F., Tsui, L. C., Rommens, J. M., Bear, C. E. et al. (1991) Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance. Cell 64, 681-691
20. Norez, C., Heda, G. D., Jensen, T., Kogan, I., Hughes, L. K., Auzanneau, C., Derand, R., Bulteau-Pignoux, L., Li, C., Ramjeesingh, M. et al. (2004) Determination of CFTR chloride channel activity and pharmacology using radiotracer flux methods. J. Cyst. Fibros. 3 (Suppl. 2), 119-121
21. Benos, D. J., Berdiev, B. K., Ismailov, I. I., Ostedgaard, L. S., Kogan, I., Li, C., Ramjeesingh, M. and Bear, C. E. (2004) Methods to study CFTR protein in vitro. J. Cyst. Fibros. 3, (Suppl. 2), 79-83
22. Kogan, I., Ramjeesingh, M., Li, C., Kidd, J. F., Wang, Y., Leslie, E. M., Cole, S. P. and Bear, C. E. (2003) CFTR directly mediates nucleotide-regulated glutathione flux. EMBO J. 22, 1981-1989
23. Gadsby, D. C., Vergani, P. and Csanady, L. (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477-483
24. Vergani, P., Basso, C., Mense, M., Nairn, A. C. and Gadsby, D. C. (2005) Control of the CFTR channel's gates. Biochem. Soc. Trans. 33, 1003-1007
25. Vergani, P., Lockless, S. W., Nairn, A. C. and Gadsby, D. C. (2005) CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature 433, 876-880
26. Wang, X., Venable, J., LaPointe, P., Hutt, D. M., Koulov, A. V., Coppinger, J., Gurkan, C., Kellner, W., Matteson, J., Plutner, H. et al. (2006) Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127, 803-815
27. Cheung, J. C., Chiaw, P. K., Pasyk, S. and Bear, C. E. (2008) Molecular basis for the ATPase activity of CFTR. Arch. Biochem. Biophys. 476, 95-100
28. Kidd, J. F., Ramjeesingh, M., Stratford, F., Huan, L. J. and Bear, C. E. (2004) A heteromeric complex of the two nucleotide binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) mediates ATPase activity. J. Biol. Chem. 279, 41664-41669
29. Kogan, I., Ramjeesingh, M., Huan, L. J., Wang, Y. and Bear, C. E. (2001) Perturbation of the pore of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits its ATPase activity. J. Biol. Chem. 276, 11575-11581
30. 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
31. Dawson, R. J. and Locher, K. P. (2006) Structure of a bacterial multidrug ABC transporter. Nature 443, 180-185
32. Dawson, R. J. and Locher, K. P. (2007) Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett. 581, 935-938