Referenced in: none

Automatically associated channels: Kv11.1

Title: Interactions between the N-terminal tail and the gating machinery of hERG K⁺ channels both in closed and open/inactive states.

Authors: Pilar de la Peña, Angeles Machín, Jorge Fernández-Trillo, Pedro Domínguez, Francisco Barros

Journal, date & volume: Pflugers Arch., 2015 Aug , 467, 1747-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25224286

Abstract
The N-terminal-most N-tail of the human ether-à-go-go-related gene (hERG) potassium channel is a crucial modulator of deactivation through its interactions with the S4-S5 loop and/or the C-linker/cNBD, leading to a stabilization of the channel's open state. Not only the N-terminal, but also the initial C-terminal region of the channel can modulate the transitions between the open and closed states either by direct or by indirect/allosteric interactions with the gating machinery. However, while a physical proximity of the N-tail to the gating machinery has been demonstrated in the closed state, data about their possible interaction in other channel conformations have been lacking. Using a site-directed cysteine mutagenesis and disulfide chemistry approach, we present here evidence that a physical proximity between the N-tail and the gating-related structures can also exist in channels held between pulses in the open/inactive state, highlighting the physiological and functional relevance of the direct interactions between the N-terminal tail and the S4-S5 loop and/or C-linker structures for modulation of channel.