Abstract
In recent years a new family of transport proteins called ABC transporters has emerged. One member of this novel family, called CFTR (cystic fibrosis transmembrane conductance regulator), has received special attention because of its association with the disease cystic fibrosis (CF). This is an inherited disorder affecting about 1 in 2000 Caucasians by impairing epithelial ion transport, particularly that of chloride. Death may occur in severe cases because of chronic lung infections, especially by Pseudomonas aeruginosa, which cause a slow decline in pulmonary function. The prospects of ameliorating the symptoms of CF and even curing the disease were greatly heightened in 1989 following the cloning of the CFTR gene and the discovery that the mutation (ΔF508), which causes most cases of CF, is localized within a putative ATP binding/ATP hydrolysis domain. The purpose of this introductory review in this minireview series is to summarize what we and others have learned during the past eight years about the structure and function of the first nucleotide binding domain (NBF1 or NBD1) of the CFTR protein and the effect thereon of disease-causing mutations. The relationship of these new findings to the pathogenesis of CF is also discussed.
Similar content being viewed by others
REFERENCES
Collins, F. S. (1992). Science 256, 774–779.
Caroll, T. P., Schiebert, E. M., and Guggino, W. B. (1993). Cell Physiol. Biochem. 3, 388–399.
Welsh, M. J., Tsuyi, L.-C., Boat, T. G., and Beaudet, A. L. (1995). In: The Metabolic Basis of Inherited Diseases (Schriber et al.) eds. McGraw-Hill, New York, pp. 3799–3876.
Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plausic, N., and Chow, J. L. (1989). Science 245, 1066–1073.
Anderson, M. P., Berger, H. A., Rich, D. P., Gregory, R. J., Smith, A. E., and Welsh, M. J. (1991). Cell 67, 775–784.
Nagel, G., Hwang, T. C., Nastiuk, K. L., Nairn, A. C., and Gadsby, D. C. (1992). Nature 360, 81–84.
Gunderson, K. L., and Kopito, R. R. (1994). J. Biol. Chem. 269, 19349–19453.
Carson, M. R., Travis, S. M., and Welsh, M. J. (1995). J. Biol. Chem. 270, 1711–1717.
Tabcharani, J. A., Chang, X.-B., Riordan, J. R., and Hanrahan, J. W. (1991). Nature 352, 628–631.
Cheng, S. H., Rich, D. P., Marshall, J., Gregory, R. J., Welsh, M. J., and Smith, A. E. (1991). Cell 66, 1027–1036.
Resin, 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, 20582–20591.
Schwiebert, 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.
Tsui, L.-C. (1992). Trends Genet. 8, 392–398.
Kerem, E., Corey, M., Kerem, B. S., Rommens, J., Mariewicz, D., Levison, H., Tsui, L.-C., and Durie, P. (1990). New Engl. J. Med. 323, 1517–1522.
Higgins, C. F. (1992). Annu. Rev. Cell. Biol. 8, 67–113.
Doige, C. A., and Ferro-Luzzi Ames, G. (1993). Annu. Rev. Microbiol. 47, 291–319.
Pedersen, P. L., and Amzel, L. M. (1993). J. Biol. Chem. 268, 9937–9940.
Walker, J. E., Saraste, M., Runswick, M. J., and Gay, N. J. (1982). EMBO J. 1, 945–951.
Shyamala, V., Baichwal, V., Beall, E., and Ames, G. F.-L. (1991). J. Biol. Chem. 266, 18714–18719.
Hyde, S., Emsley, P., Hartshorn, M. J., Mimmack, M. M., Gileadi, U., Pearce, S. R., Gallagher, M. P., Gill, D. R., Hubbard, R. E., and Higgins, C. F. (1990). Nature 346, 362–365.
Mimura, C. S., Holbrook, S. R., and Ames, G. F.-L. (1991). Proc. Natl. Acad. Sci. USA 88, 84–88.
Logan, J., Hiestrand, D., Daram, P., Huang, Z., Muccio, D. D., Hartman, J., Haley, B., Cook, W. J., and Sorscher, E. J. (1994). J. Clin. Invest. 94, 228–236.
Schulz, G. E., Elzinga, M., Marx, F., and Schirmer, R. H. (1974). Nature 250, 120–123.
Sachsenheimer, W., and Schulz, G. E. (1977). J. Mol Biol. 114, 23–36.
Fry, D. C., Kuby, S. A., and Mildvan, A. S. (1986). Proc. Natl. Acad. Sci. 83, 907–911.
Mildvan, A. S. (1989). FASEB J. 3, 1705–1714.
Story, R. M., and Steitz, T. A. (1992). Nature 355, 374–376.
Bianchet, M., Ysern, S., Hullihen, J., Pedersen, P. L., and Amzel, L. M. (1991). J. Biol. Chem. 266, 21197–21201.
Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994). Nature 370, 621–628.
Bianchet, M. A., Hullihen, J., Pedersen, P. L., and Amzel, L. M. (1997). Submitted.
Bianchet, M. A., Ko, Y. H., Amzel, L. M., and Pedersen, P. L. (1997). J. Bioenerg. Biomembr. 29, 503–523.
Ohtsubo, M., Yoshida, M., Ohta, S. Kagawa, Y., Yohda, M., and Date, T. (1987). Biochem. Biophys. Res. Commun. 146, 705–710.
Parsonage, D., Wilke-Mounts, S., and Senior, A. E. (1988). FEBS Lett. 232, 111–114.
Manavalin, P., Dearborn, D. G., McPherson, J. M., and Smith. A. E. (1995). FEBS Lett. 366, 87–91.
Thomas, P. J., Shenbagamurthi, P., Ysern, X., and Pedersen, P. L. (1991). Science 251, 555–557.
Ko, Y. H., Thomas, P. J., and Pedersen, P. L. (1993). J. Biol. Chem. 268, 24330–24338.
Hartman, J., Huang, Z., Rado, T. A., Peng, S., Jilling, T., Muccio, D. D., and Sorscher, E. J. (1992). J. Biol. Chem. 267, 6455–6458.
Anderson, M. P., and Welsh, M. J. (1992). Science 257, 1701–1704.
Smit, L. S., Wilkinson, D. J., Mansoura, M. K., Collings, F. S., and Dawson, D. C. (1993). Proc. Natl. Acad. Sci. USA 90, 9963–9967.
Quinton, P. M., and Reddy, M. M. (1992). Nature 360, 79–81.
Bell, C. L., and Quinton, P. M. (1993). Am. J. Physiol. 264, C925–C931.
Ko, Y. H., and Pedersen, P. L. (1995). J. Biol. Chem. 268, 24330–24338.
Pedersen, P. L., Hullihen, J., Bianchet, M., Amzel, L. M., and Lebowitz, M. S. (1995). J. Biol. Chem. 270, 1775–1784.
Al-Shawi, M. K., Parsonage, D., and Senior, A. E. (1990). J. Biol. Chem. 265, 5595–5601.
Bear, C. E., Li, C., Galley, K., Wang, Y., Garami, E., and Ramjeesingh, M. (1997). J. Bioenerg. Biomembr. 29, 465–474.
Carson, M. R., and Welsh, M. J. (1995). Biophys. J. 69, 2443–2448.
Gadsby, D. C., and Nairn, A. C. (1994). Trends Biochem. Sci. 19, 513–518.
Thomas, P. J., Shenbagamurthi, P., Sondek, J., Hullihen, J. M., and Pedersen, P. L. (1992). J. Biol. Chem. 267, 5727–5730.
Thomas, P. J., and Pedersen, P. L. (1993). J. Bioenerg. Biomembr. 25, 11–19.
Rich, D. P., Anderson, M. P., Gregory, R. J., Cheng, S. H., Paul, S. Jefferson, D. M., McCann, J. D., Klinger, K. W., Smith, A. E., and Welsh, M. J. (1990). Nature 347, 358–363.
Anderson, M. P., Rich, D. P., Gregory, R. J., Smith, A. E., and Welsh, M. J. (1991). Science 251, 679–682.
Denning, G. M., Ostedguard, L. S., and Welsh, M. J. (1992). J. Cell Biol. 118, 551–559.
Cheng, S. H., Gregory, R., Marshall, J., Paul, S., Souza, D. W, White, G. A., O'Riordan, C. R., and Smith, A. E. (1990). Cell 63, 827–834.
Li, C., Ramjeesigh, M., Reyers, E., Jensen, T., Chang, X., Rommens, J. M., and Bear, C. E. (1993). Nature Genet. 3, 311–316.
Drumm, M. L., Wilkinson, D. J., Smit, L. S., Worrell, R. T., Strong, T. V., Frizzell, R. A., Dawson, D. C., and Collins, F. S. (1991). Science 254, 1797–1800.
Denning, G. Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., and Welsh, M. J. (1992). Nature 358, 761–764.
Thomas, P. J., Ko, Y. H., and Pedersen, P. L. (1992). FEBS Lett. 312, 7–9.
Pasyk, E. A., and Foskett, J. K. (1995). J. Biol. Chem. 270, 12347–12350.
Ward, C. L., and Kopito, R. R. (1994). J. Biol. Chem. 269, 25710–25718.
Lukacs, G. L., Mohamed, A., Kartner, N., Chang, X.-B., Riordan, J. R., and Grinstein, S. (1994). EMBO J. 13, 6076–6086.
Yang, Y., Janich, S., Cohn, J., and Wilson, J. M. (1993). Proc. Natl. Acad. Sci. USA 90, 9480–9484.
Strickland, E., Qu, B.-H., Millen, L., and Thomas, P. J. (1997). J. Biol. Chem. 272, in press.
Brown, C. R., Hong-Brown, L. Q., and Welch, W. J. (1997). J. Clin. Invest., in press.
Sato, S., Ward, C. L., Krouse, M. E., Wine, J. J., and Kopito, R. R. (1996). J. Biol. Chem. 271, 635–638.
Brown, C. R., Hong-Brown, L. Q., and Welch, W. J. (1997). J. Bioenerg. Biomembr. 29, 491–502.
Chang, S.-B., Hou, Y.-X., Jensen, T. J., and Riordan, J. R. (1994). J. Biol. Chem. 269, 18572–18475.
Welsh, M. J., and Smith, A. E. (1993). Cell 73, 1251–1254.
Arispe, N., Rojas, E., Hartman, J., Sorscher, E. J., and Pollard, H. B. (1992). Proc. Natl. Acad. Sci. USA 89, 1539–1543.
Baichwal, V., Liu, D., and Ames, G. F.-L. (1993). Proc. Natl. Acad. Sci. USA 90, 620–624.
Ko, Y. H., Delannoy, M., and Pedersen, P. L. (1997). Biochemistry 36, 5053–5064.
Gruis, D. B., and Price, E. M. (1997). Biochemistry 36, 7739–7745.
Cutting, G. R. (1993). J. Bioenerg. Biomembr. 25, 7–10.
Ko, Y. H., Thomas, P. J., and Pedersen, P. L. (1994). J. Biol. Chem. 269, 14584–14588.
Randak, C., Roscher, A. A., Hadorn, H.-B., Assfalg-Machleidt, I., Averswald, E. A., and Machleidt, W. (1995). FEBS Lett. 363, 189–194.
Sheppard, D. N., Ostergaard, L. S., Rich, D. R., and Welsh, M. J. (1994). Cell 76, 1091–1098.
Dulhanty, A. M., and Riordan, J. R. (1994). Biochemistry 33, 4072–4079.
Lu, T. N., and Pedersen, P. L. (1997). To Be Submitted.
Chang, X. B., Tabcharani, J. A., Hou, Y. X., Jensen, T. J., Kartner, N., Alan, N., Hanrahan, J. W., and Riordan, J. R. (1993). J. Biol. Chem. 268, 11304–11311.
Eisner, T., and Meinwald, J. (1996). Proc. Natl. Acad. Sci. USA 92, 1–8.
Daly, J. W. (1995). Proc. Natl. Acad. Sci. USA 92, 9–18.
Boeman, H. G. (1991). Cell 65, 205–207.
Bevins, C. L., and Zasloff, M. (1990). Annu. Rev. Biochem. 59, 395–414.
Lehrer, R. I., Lichtenstein, A. K., and Ganz, T. (1993). Annu. Rev. Immunol. 11, 105–128.
Kagan, B. L., Selsted, M. E., Ganz, T., and Lehrer (1990). Proc. Natl. Acad. Sci. USA 87, 210–214.
Lehrer, R. I., Ganz, T., Selsted, M. E., Babior, B. M., and Curnutte, J. T. (1988). Ann. Intern. Med. 109, 127–142.
Ganz, T., Selsted, M. D., Szklarek, D., Harwig, S. S. L., Daher, K., and Lehrer, R. I. (1985). J. Clin. Invest. 76, 1427–1435.
Selsted, M. E., Brown, D. M., DeLange, R. J., and Lehrer, R. I. (1983). J. Biol. Chem. 258, 14485–14489.
Habermann, E. (1972). Science 177, 314–322.
Kaiser, E. T., and Kezdy, F. J. (1987). Ann. Rev. Biophys. Chem. 16, 561–581.
Zasloff, M. (1987). Proc. Natl. Acad. Sci. USA 85, 910–913.
Zasloff, M., Martin, B., and Chen, H.-Ch. (1988). Proc. Natl. Acad. Sci. USA 85, 910–913.
Sessa, G., Freer, J. H., Colacicco, G., and Weismann, G. (1969). J. Biol. Chem. 244, 3575–3582.
Ludthe, S. J., He, K., Heller, W. T. Harroun, T. A., Yang, L., and Huang, H. W. (1996). Biochemistry 35, 13723–13728.
Zar, H., Saiman, L., Quittell, L., and Prince, A. (1995). J. Pediatrics 126, 230–233.
Imundo, L., Barasch, J., Prince, A., and Al-Awquati, Q. (1995). Proc. Natl. Acad. Sci. USA. 92, 3019–3023.
Pier, G. B., Grout, M., Zaidi, T. S., Olsen, J. C. Johnson, L. G. Yankaskas, J. R., and Goldberg, J. B. (1996). Science 271, 64–67.
Smith, J. J., Travis, S. M., Greenberg, E. P., and Welsh, M. J. (1996). Cell 85, 229–236.
Goldman, M. J., Anderson, G. M., Stolzenberg, E. D., Prasad Kari, U., Zasloff, M., and Wilson, J. M. (1997). Cell 88, 553–560.
Diamond, G., Zasloff, M., Eck, H., Brasseur, M., Maloy, W. L., and Bevins, C. L. (1991). Proc. Natl. Acad. Sci. USA 88, 3952–3956.
Ko, Y. H., Delannoy, M., and Pedersen, P. L. (1997). FEBS Lett. 405 200–208.
Bao-He, Q., Strickland, E., and Thomas, P. J. (1997). J. Bioenerg. Biomembr. 29, 483–490.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ko, Y.H., Pedersen, P.L. Frontiers in Research on Cystic Fibrosis: Understanding Its Molecular and Chemical Basis and Relationship to the Pathogenesis of the Disease. J Bioenerg Biomembr 29, 417–427 (1997). https://doi.org/10.1023/A:1022402105375
Issue Date:
DOI: https://doi.org/10.1023/A:1022402105375