Physical and Functional Interaction Sites in Cytoplasmic Domains of KCNQ1 and KCNE1 Channel Subunits.

Physical and Functional Interaction Sites in Cytoplasmic Domains of KCNQ1 and KCNE1 Channel Subunits. Am J Physiol Heart Circ Physiol. 2019 Dec 13;: Authors: Chen J, Liu Z, Creagh JP, Zheng R, McDonald TV Abstract The cardiac potassium IKs current is carried by a channel complex formed from a-subunits encoded by KCNQ1 and b-subunits encoded by KCNE1. Deleterious mutations in either gene are associated with hereditary long QT syndrome. Interactions between the transmembrane domains of the a- and b-subunits determine the activation kinetics of IKs. A physical and functional interaction between C-termini of the proteins has also been identified that impacts deactivation rate and voltage-dependence of activation. We sought to explore the specific physical interactions between the C-termini of the subunits that confer such control. Hydrogen/deuterium exchange coupled to mass spectrometry narrowed down the region of interaction to KCNQ1 residues 352-374 and KCNE1 residues 70-81, and provided evidence of secondary structure within these segments. Key mutations of residues in these regions tended to shift voltage dependence of activation toward more depolarizing voltages. Double mutant cycle analysis then revealed energetic coupling between KCNQ1-I368 and KCNE1-D76 during channel activation. Our results suggest that the proximal C-terminal regions of KCNQ1 and KCNE1 participate in a physical and functional interaction during channel opening ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research