Skip to main content
Log in

Coupling of ATP Hydrolysis with Channel Gating by Purified, Reconstituted CFTR

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel situated on the apical membrane of epithelial cells. Our recent studies of purified, reconstituted CFTR revealed that it also functions as an ATPase and that there may be coupling between ATP hydrolysis and channel gating. Both the ATP turnover rate and channel gating are slow, in the range of 0.2 to 1 s−1, and both activities are suppressed in a disease-causing mutation situated in a putative nucleotide binding motif. Our future studies using purified protein will be directed toward understanding the structural basis and mechanism for coupling between hydrolysis and channel function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Anderson, M., and M. J. Welsh (1992). Science 257, 1701–1704.

    Google Scholar 

  • Anderson, M., Berger, H., Rich, D., Gregory R., Smith, A., and Welsh, M. (199la). Cell 67, 775–784.

  • Anderson, M., Gregory, R., Thompson, S., Souza, D., Paul, S., Mulligan, R., Smith, A., and Welsh, M. (1991b). Science 253, 202–205.

    Google Scholar 

  • Baukrowitz, T., Hwang, T., Nairn, A., and Gadsby, D. (1994). Neuron 12, 473–482.

    Google Scholar 

  • Bear, C., and Reyes, E. (1992). Am. J. Physiol. 262, C251–C256.

    Google Scholar 

  • Bear, C., Li, C., Kartner, N., Bridges, R., Jensen, T., Ramjeesingh, M., and Riordan, J. (1992). Cell 68, 809–818.

    Google Scholar 

  • Berger, H. A., Travis, S. M., and Welsh, M. J. (1993). J. Biol. Chem. 268, 2037–2047.

    Google Scholar 

  • Bourne, H. R., Sanders, D. A., and McCormick, F. (1991). nature 349, 117–120.

    Google Scholar 

  • Carson, M., and Welsh, M. (1993). Am. J. Physiol. 265, L27–L32.

    Google Scholar 

  • Chang, X.-B., Tabcharani, J., Hou, Y.-X., Jensen, T., Kartner, N., Alon, N., Hanrahan, J., and Riordan, J. (1993). J. Biol. Chem. 268, 11304–11311.

    Google Scholar 

  • Cheng, S., Rich, D., Marshall, J., Gregory, R., Welsh, M., and Smith, A. (1991). Cell 66, 1027–1036.

    Google Scholar 

  • Dousmanis, A. G., Nairn, A. C., and D. C. Gadsby (1996). Biophys. J. 70, A127.

    Google Scholar 

  • Dulhanty, A. M., and Riordan, J. R., (1994). Biochemistry 33(13), 4072–4079.

    Google Scholar 

  • Frizzell, R. A., Field, M., and Schultz, S. G. (1979). Am. J. Physiol. 236, F1–F8.

    Google Scholar 

  • Gabriel, S. E., Clarke, L. L., Boucher, R. C., and Stutts, M. J., (1993). Nature 363, 263–266.

    Google Scholar 

  • Gout, I., Dhand, R., Hiles, I., Fry, M., Panayotou, G., Das, P., Truong, O., Totty, N., Hsuan, J., Booker, G., Campbell, I., and Waterfield, M. (1993). Cell 75, 25–36.

    Google Scholar 

  • Gunderson, K. L., and Kopito, R. R. (1994). J. Biol. Chem. 269, 19349–19353.

    Google Scholar 

  • Gunderson, K. L., and Kopito, R. R. (1995). Cell 82, 231–239.

    Google Scholar 

  • Hartman, J., Huang, Z., Rado, T., Peng, S., Jilling, T., Muccio, D., and Sorscher, E. (1992). J. Biol. Chem. 267, 6455–6458.

    Google Scholar 

  • Haws, C., Krouse, M. E., Xia, Y., Gruenert, D. C., and Wine, J. J. (1992). Am. J. Physiol. 263 (6 Pt. 1), L692–707.

    Google Scholar 

  • Hwang, T.-C., Nagel, G., Nairn, A., and Gadsby, D. (1994). Proc. Natl. Acad. Sci. USA 91, 4698–4702.

    Google Scholar 

  • Hyde, S., Emsley, P., Hartshorn, M., Mimmack, M., Gileadi, U., Pearce, S., Gallanger, M., Gill, D., Hubbard, R., and Higgins, C. (1990). Nature 346, 362–365.

    Google Scholar 

  • Inagaki, N., Gonoi, T., Clement, J., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seina, S., and Bryan, J. (1995). Science 270, 1166–1169.

    Google Scholar 

  • Kartner, N., Hanrahan, J., Jensen, T., Naismith, L., Sun, S., Ackerley, C., Reyes, E., L-C. Tsui, Rommens, J. M., Bear, C. E., and Riordan, J. R. (1991). Cell 64, 681–691.

    Google Scholar 

  • Knowles, M. R., Clarke, L. L., and Boucher, R. C. (1991). N. Engl. J. Med. 325, 533–538.

    Google Scholar 

  • Ko, Y. H., and Pedersen, P. (1995). J. Biol. Chem. 270, 22093–22096.

    Google Scholar 

  • Ko, Y. H., Thomas, P. J., and Pedersen, P. L. (1994). J. Biol. Chem. 269(20), 14584–14588.

    Google Scholar 

  • Li, C., Ramjeesingh, M., and Bear, C. E. (1996a). J. Biol. Chem. 271, 11623–11626.

    Google Scholar 

  • Li, C., Ramjeesingh, M., Wang, W., Garami, E., Hewryk, M., Lee, D., Rommens, J. M., Galley, K., and Bear, C. E. (1996b). J. Biol. Chem. 271, 28463–28468.

    Google Scholar 

  • Loo, T. W., and Clarke, D. M. (1995). J. Biol. Chem. 270, 21449–21452.

    Google Scholar 

  • Ma, J., Tasch, J. E., Tao, T., Zhao, J., Xie, J., Drumm, M. L., and Davis, P. B., (1996). J. Biol. Chem. 271(13) 7351–6.

    Google Scholar 

  • Manavalan, P., Dearborn, D., McPherson, J., and Smith, A. (1995). FEBS Lett. 366, 87–91.

    Google Scholar 

  • Mimura, C., Holbrook, S., and Ames, G. (1991). Proc. Natl. Acad. Sci. USA 88, 84–88.

    Google Scholar 

  • Prince, L. S., Workman, R. B., Jr., and Marchase, R. B. (1994). Proc. Natl. Acad. Sci. USA 91, 5192–5196.

    Google Scholar 

  • Quinton, P., and Reddy, M. (1992). Nature 360, 79–81.

    Google Scholar 

  • Racker, E. (1985). Reconstitution of Transporters, Receptors, and Pathological States, Academic Press, Orlando, Florida, Chapter 2, p. 37.

    Google Scholar 

  • Ramjeesingh, M., Li, C., Wang, W., and Bear, C. E. (1995). Ped. Pulmonol. S12, A33.

    Google Scholar 

  • Reisin, I. L., Prat, A. G., Abraham, E. H., Amara, J. F., Gregory, R. J., Ausiello, D. A., and Cantiello, H. F. (1994). J. Biol. Chem. 269, 20584–20591.

    Google Scholar 

  • Riordan, J., Rommens, J., Kerem, B.-S., Noa, A., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Jia-Ling Chou, Drumm, M., lannuzzi, M., Collins, F., and Tsui, L.-C. (1989). Science 245, 1066–1073.

    Google Scholar 

  • Rozmahel, R., Wilschanski, M., Plyte, S., Oliver, N., Auerbach, W., Moore, A., Wuerst, W., Joyner, A., Firstner, J., Durie, P., Bear, C., and Tsui, L-C. (1996). Nature Genet. 12(3), 280–287.

    Google Scholar 

  • Schweibert, E. M., Egan, M. E., Hwang, T-H., Fulmer, S. B., Allen, S. S., Cutting, G. R., and Guggino, W. B. (1995). Cell 81, 1063–1073.

    Google Scholar 

  • Senior A. E., al-Shawi, M. K., and Urbatsch, I. L. (1995a). J. Bioenerg. Biomembr. 27, 31–36, ??

    Google Scholar 

  • Senior, A. E., al-Shawi, M. K., and Urbatsch, I. L. (1995b). FEBS Lett. 377(3), 285–289.

    Google Scholar 

  • Shapiro, A. B., and Ling, V. (1994). J. Biol. Chem. 269, 3745–3754.

    Google Scholar 

  • Shaprio, A. B., and Ling, V. (1995). J. Biol. Chem. 270, 16167–16175.

    Google Scholar 

  • Sharom, F., Xiaohong, Y., J, C., and CA, Doige. (1995a). Biochem. J. 308, 381–390.

    Google Scholar 

  • Sharom, F. J. Sharom, DiDiodato, G., Yu, Xiaohong, and Ashbourne, K. J. D. (1995b). J. Biol. Chem. 270, 10334–10341.

    Google Scholar 

  • Snouwaert, J. N., Brigman, K. K., Latour, A. M., Malouf, N. N., Boucher, R. C., Smithies, O., and Koller, B. H. (1992). Science 257, 1083–1088.

    Google Scholar 

  • Stutts, M. J., Fitz, J. G., Paradiso, A. M., and Boucher, R. C. (1994). Am. J. Physiol. 267, C1442–C1451.

    Google Scholar 

  • Stutts, M. J., Canessa, C. M., Olsen, J. C., Hamrick, M., Cohn, J. A., Rossier, B. C., and Boucher, R. C. (1995). Science 269, 847–850.

    Google Scholar 

  • Tabcharani, J., Lowe, W., Elie, D., and Hanrahan, J. (1990). FEBS Lett 270, 157–164.

    Google Scholar 

  • Tabcharani, J. A., Chang, X.-B., Riordan, J. R., and Hanrahan, J. W. (1991). Nature 352, 628–631.

    Google Scholar 

  • Tabcharani, J. A., Chang, X.-B., Riordan, J. R., and Hanrahan, J. W. (1992). Biophys. J. 62, 1–4.

    Google Scholar 

  • Tabcharani, J., Rommens, J., Hou, Y., Chang, X.-B., Tsui, L., Riordan, J., and Hanrahan, J. (1993). Nature 366, 79–82.

    Google Scholar 

  • Thomas, P., Shenbagamurthi, T., Ysern, X., and Pedersen, P. (1991). Science 251, 555–557.

    Google Scholar 

  • Travis, S., Carson, M., Ries, D., and Welsh, M. (1993). J. Biol. Chem. 268, 15336–15339.

    Google Scholar 

  • Tsui, L. (1995). Am. J. Resp. Crit. Care Med. 151, S47–53.

    Google Scholar 

  • Warshaw, D. M. (1996). News Physiol. Sci. 11, 1–7.

    Google Scholar 

  • Welsh, M., Tsui, L.-C., Boat, T. F., and Beaudet, A. L. (1995). Cystic Fibrosis in the Metabolic and Molecular Bases of Inherited Disease, 7th edn. (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds.), McGraw-Hill, New York, pp. 3799–3876.

    Google Scholar 

  • Winter, M., Sheppard, D., Carson, M., and Welsh, M. (1994). Biophys. J. 66, 1398–1403.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bear, C.E., Li, C., Galley, K. et al. Coupling of ATP Hydrolysis with Channel Gating by Purified, Reconstituted CFTR. J Bioenerg Biomembr 29, 465–473 (1997). https://doi.org/10.1023/A:1022435007193

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022435007193

Navigation