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J Cyst Fibros. 2013 Dec;12(6):737-45. doi: 10.1016/j.jcf.2013.02.002. Epub 2013 Mar 9.

CFTR: effect of ICL2 and ICL4 amino acids in close spatial proximity on the current properties of the channel.

Author information

1
Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS, Poitiers, France.

Abstract

BACKGROUND:

CFTR is the only ABC transporter functioning as a chloride (Cl(-)) channel. We studied molecular determinants, which might distinguish CFTR from standard ABC transporters, and focused on the interface formed by the intracellular loops from the membrane spanning domains.

METHODS:

Residues from ICL2 and ICL4 in close proximity were targeted, and their involvement in the functioning of CFTR was studied by whole cell patch clamp recording.

RESULTS:

We identified 2 pairs of amino acids, at the extremity of the bundle formed by the four intracellular loops, whose mutation i) decreases the Cl(-) current of CFTR (couple E267-K1060) or ii) increases it with a change of the electrophysiological signature (couple S263-V1056).

CONCLUSIONS:

These results highlight the critical role of these ICL residues in the assembly of the different domains and/or in the Cl(-) permeation pathway of CFTR.

KEYWORDS:

ABC transporter; CFTR; Channel gating; ICL; Structure-function

PMID:
23478129
DOI:
10.1016/j.jcf.2013.02.002
[Indexed for MEDLINE]
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