Neuron
Volume 13, Issue 3, September 1994, Pages 623-634
Journal home page for Neuron

Article
Novel pore-lining residues in CFTR that govern permeation and open-channel block

https://doi.org/10.1016/0896-6273(94)90030-2Get rights and content

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is both a member of the ATP-binding cassette superfamily and a Cl-selective ion channel. We investigated the permeation pathway of human CFTR with measurements on conduction and open-channel blockade by diphenylamine-2-carboxylic acid (DPC). We used site-directed mutagenesis and oocyte expression to locate residues in transmembrane domain (TM) 6 and TM 12 that contact DPC and control rectification and single-channel conductances. Thus, TM 12 and the previously investigated TM 6 line the CFTR pore. In each TM, residues in contact with DPC are separated by two turns of an a helix. The contributions of TM 6 and TM 12 to DPC block and C permeation, however, are not equivalent. The resulting structural model for the conduction pathway may guide future studies of permeation in other C channels and ATP-binding cassette transporters

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