Unknown

Dataset Information

0

Two salt bridges differentially contribute to the maintenance of cystic fibrosis transmembrane conductance regulator (CFTR) channel function.


ABSTRACT: Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg(352)-Asp(993) and Arg(347)-Asp(924), that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg(347) not only interacts with Asp(924) but also interacts with Asp(993). The tripartite interaction Arg(347)-Asp(924)-Asp(993) mainly contributes to maintaining a stable s2 open subconductance state. The Arg(352)-Asp(993) salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg(352) and Asp(993), channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle.

SUBMITTER: Cui G 

PROVIDER: S-EPMC3711338 | BioStudies | 2013-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1999-01-01 | S-EPMC103773 | BioStudies
2010-01-01 | S-EPMC2862207 | BioStudies
2014-01-01 | S-EPMC4110316 | BioStudies
1000-01-01 | S-EPMC4906143 | BioStudies
2002-01-01 | S-EPMC1222885 | BioStudies
1992-01-01 | S-EPMC1132708 | BioStudies
2017-01-01 | S-EPMC5302377 | BioStudies
2005-01-01 | S-EPMC553306 | BioStudies
2015-01-01 | S-EPMC4429351 | BioStudies
1000-01-01 | S-EPMC297657 | BioStudies