Mechanistic insight into human ether-a-go-go-related gene (hERG) K+ channel deactivation gating from the solution structure of the EAG domain.

ABSTRACT: Human ether-à-go-go-related gene (hERG) K(+) channels have a critical role in cardiac repolarization. hERG channels close (deactivate) very slowly, and this is vital for regulating the time course and amplitude of repolarizing current during the cardiac action potential. Accelerated deactivation is one mechanism by which inherited mutations cause long QT syndrome and potentially lethal arrhythmias. hERG deactivation is highly dependent upon an intact EAG domain (the first 135 amino acids of the N terminus). Importantly, deletion of residues 2-26 accelerates deactivation to a similar extent as removing the entire EAG domain. These and other experiments suggest the first 26 residues (NT1-26) contain structural elements required to slow deactivation by stabilizing the open conformation of the

SUBMITTER: Muskett FW 

PROVIDER: S-EPMC3057830 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature