Spatial positioning of CFTR's pore-lining residues affirms an asymmetrical contribution of transmembrane segments to the anion permeation pathway.

ABSTRACT: The structural composition of CFTR's anion permeation pathway has been proposed to consist of a short narrow region, flanked by two wide inner and outer vestibules, based on systematic cysteine scanning studies using thiol-reactive probes of various sizes. Although these studies identified several of the transmembrane segments (TMs) as pore lining, the exact spatial relationship between pore-lining elements remains under debate. Here, we introduce cysteine pairs in several key pore-lining positions in TM1, 6, and 12 and use Cd(2+) as a probe to gauge the spatial relationship of these residues within the pore. We find that inhibition of single cysteine CFTR mutants, such as 102C in TM1 or 341C in TM6, by intracellular Cd(2+) is readily reversible upon removal of the metal ion. However, the

SUBMITTER: Gao X 

PROVIDER: S-EPMC4845689 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature