Referenced in: none

Automatically associated channels: Kir3.2

Title: Inverse agonist-like action of cadmium on G-protein-gated inward-rectifier K(+) channels.

Authors: Atsushi Inanobe, Takanori Matsuura, Atsushi Nakagawa, Yoshihisa Kurachi

Journal, date & volume: Biochem. Biophys. Res. Commun., 2011 Apr 8 , 407, 366-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21396912

Abstract
The gate at the pore-forming domain of potassium channels is allosterically controlled by a stimulus-sensing domain. Using Cd²(+) as a probe, we examined the structural elements responsible for gating in an inward-rectifier K(+) channel (Kir3.2). One of four endogenous cysteines facing the cytoplasm contributes to a high-affinity site for inhibition by internal Cd²(+). Crystal structure of its cytoplasmic domain in complex with Cd²(+) reveals that octahedral coordination geometry supports the high-affinity binding. This mode of action causes the tethering of the N-terminus to CD loop in the stimulus-sensing domain, suggesting that their conformational changes participate in gating and Cd²(+) inhibits Kir3.2 by trapping the conformation in the closed state like "inverse agonist".