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The ABC protein turned chloride channel whose failure causes cystic fibrosis

Nature volume 440, pages 477–483 (2006)Cite this article

Abstract

CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. New structural and biochemical information from prokaryotic ABC proteins and functional information from CFTR channels has led to a unifying mechanism explaining those ATP-driven conformational changes.

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Figure 1: Opening and closing of CFTR channels.
Figure 2: Possible structure and organization of domains in CFTR.
Figure 3: The conserved Walker A lysine is critical for ATP binding in each NBD.
Figure 4: ATP hydrolysis prompts channel closure.
Figure 5: Structures of the MalK homodimer.

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Acknowledgements

This review and our research on CFTR were supported by grants from the NIH and Fogarty International Center (to D.C.G). We dedicate this review to our late colleague Benjamin Angel, MA, MB BS (3rd December 1978 to 2nd October 2005), whose courage and grace in the face of CF continue to inspire us.

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Authors and Affiliations

  1. Laboratory of Cardiac/Membrane Physiology, The Rockefeller University, New York, 10021, NY, USA

    David C. Gadsby

  2. Department of Pharmacology, University College London, London, WC1E 6BT, UK

    Paola Vergani

  3. Department of Medical Biochemistry, Semmelweis University, 1444 Budapest, Pf. 262, Hungary

    László Csanády

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Correspondence to David C. Gadsby.

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Gadsby, D., Vergani, P. & Csanády, L. The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477–483 (2006). https://doi.org/10.1038/nature04712

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