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Structure and Function of the CFTR Chloride Channel
Journal article   Open access   Peer reviewed

Structure and Function of the CFTR Chloride Channel

DAVID N. Sheppard and MICHAEL J. Welsh
Physiological reviews, Vol.79(1), pp.S23-S45
01/01/1999
DOI: 10.1152/physrev.1999.79.1.S23
PMID: 9922375
url
https://doi.org/10.1152/physrev.1999.79.1.S23View
Published (Version of record) Open Access

Abstract

Sheppard, David N., and Michael J. Welsh. Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79 , Suppl.: S23–S45, 1999. — The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl− channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic disease cystic fibrosis. The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function. The MSDs form the channel pore, phosphorylation of the R domain determines channel activity, and ATP hydrolysis by the NBDs controls channel gating. Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.

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