Probing the structural and functional domains of the CFTR chloride channel.

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 alpha-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.

journal_name

J Bioenerg Biomembr

authors

Akabas MH,Cheung M,Guinamard R

doi

10.1023/a:1022482923122

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

453-63

issue

5

eissn

0145-479X

issn

1573-6881

journal_volume

29

pub_type

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