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Probing the Structural and Functional Domains of the CFTR Chloride Channel

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Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) forms an anion-selective channel involved in epithelial chloride transport. Recent studies have provided new insights into the structural determinants of the channel's functional properties, such as anion selectivity, single-channel conductance, and gating. Using the scanning-cysteine-accessibility method we identified 7 residues in the M1 membrane-spanning segment and 11 residues in and flanking the M6 segment that are exposed on the water-accessible surface of the protein; many of these residues may line the ion-conducting pathway. The pattern of the accessible residues suggests that these segments have a largely α-helical secondary structure with one face exposed in the channel lumen. Our results suggest that the residues at the cytoplasmic end of the M6 segment loop back into the channel, narrowing the lumen, and thereby forming both the major resistance to ion movement and the charge-selectivity filter.

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Authors and Affiliations

  1. Departments of Physiology and Cellular Biophysics and Medicine, Columbia University, New York, NY, 10032

    Myles H. Akabas

  2. Center for Molecular Recognition, Columbia University, New York, NY, 10032

    Myles H. Akabas, Min Cheung & Romain Guinamard

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  1. Myles H. Akabas
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Akabas, M.H., Cheung, M. & Guinamard, R. Probing the Structural and Functional Domains of the CFTR Chloride Channel. J Bioenerg Biomembr 29, 453–463 (1997). https://doi.org/10.1023/A:1022482923122

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