PubMed 23839156

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv1.4 , Kv1.5 , Kv3.1 , Kv4.3 , Kv7.1 , Slo1

Title: A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels.

Authors: Nathalie Strutz-Seebohm, Ulrike Henrion, Nicole Schmitt, Eric Schulze-Bahr, Guiscard Seebohm

Journal, date & volume: Cell. Physiol. Biochem., 2013 , 31, 968-80

PubMed link:

Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels.Here, we study the impact of these residues on ion selectivity, permeation and inactivation kinetics as well as the modulation by β-subunits using site-specific mutagenesis, electrophysiological analyses and molecular dynamics simulations.We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels.We propose a model in which structural changes accompanying activation and β-subunit modulation allosterically constrain the backbone carbonyl oxygen atoms via the side chain of the respective X-residue in the signature sequence to reduce conductance during slow inactivation.