Unveiling the Gating Mechanism of CRAC Channel: A Computational Study.

ABSTRACT: CRAC channel is ubiquitous and its importance in the regulation of the immune system is testified by the severe immunodeficiencies caused by its mutations. In this work we took advantage of the availability of open and closed structures of this channel to run for the first time simulations of the whole gating process reaching the relevant time-scale with an enhanced sampling technique, Targeted Molecular Dynamics. Our simulations highlighted a complex allosteric propagation of the conformational change from peripheral helices, where the activator STIM1 binds, to the central pore helices. In agreement with mutagenesis data, our simulations revealed the key role of residue H206 whose displacement creates an empty space behind the hydrophobic region of the pore, thus releasing a steric brake

SUBMITTER: Guardiani C 

PROVIDER: S-EPMC8712694 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature