Conformational changes opening and closing the CFTR chloride channel: Insights from cysteine scanning mutagenesis

被引:9
作者
El Hiani, Yassine [1 ]
Linsdell, Paul [1 ]
机构
[1] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS B3H 4R2, Canada
基金
加拿大健康研究院;
关键词
CFTR; gate; cystic fibrosis; chloride channel; TRANSMEMBRANE CONDUCTANCE REGULATOR; CYTOPLASMIC LOOP 3; CYSTIC-FIBROSIS; ABC TRANSPORTER; CL-CHANNEL; ALTERNATING ACCESS; POSITIVE CHARGES; PORE; DOMAIN; REVEALS;
D O I
10.1139/bcb-2014-0038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cystic fibrosis, the most common lethal genetic disease affecting young people in North America, is caused by failure of the chloride ion channel known as CFTR (cystic fibrosis transmembrane conductance regulator). CFTR belongs to the large family of ATP-binding cassette (ABC) membrane transporters. In CFTR, ATP-driven events at the nucleotide-binding domains (NBDs) open and close a gate that controls chloride permeation. However, the conformational changes concomitant with opening and closing of the CFTR gate are unknown. Diverse techniques including substituted cysteine accessibility method, disulfide cross-linking, and patch-clamp recording have been used to explore CFTR channel structure. Here, we consider the architecture of both the open and the closed CFTR channel. We review how CFTR channel structure changes between the closed and the open channel conformations and portray the relative function of both cytoplasmic and vestigial gates during the gating cycle. Understanding how the CFTR channel gates chloride permeation is central for understanding how CFTR defects lead to CF. Such knowledge opens the door for novel ways to maximize CFTR channel activity in a CF setting.
引用
收藏
页码:481 / 488
页数:8
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