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Cell Physiol Biochem. 2013;31(6):968-80. doi: 10.1159/000350115. Epub 2013 Jun 26.

A common structural component for β-subunit mediated modulation of slow inactivation in different KV channels.

Author information

1
Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.

Abstract

BACKGROUND/AIMS:

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.

METHODS:

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.

RESULTS:

We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels.

CONCLUSION:

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.

PMID:
23839156
DOI:
10.1159/000350115
[Indexed for MEDLINE]
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