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- Title
A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different K<sub>V</sub> Channels.
- Authors
Strutz-Seebohm, Nathalie; Henrion, Ulrike; Schmitt, Nicole; Schulze-Bahr, Eric; Seebohm, Guiscard
- 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. Copyright © 2013 S. Karger AG, Basel
- Subjects
PHYSIOLOGICAL effects of potassium channels; ION channels; ELECTROPHYSIOLOGY; MUTAGENESIS; CARBONYL compounds; ALLOSTERIC proteins
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2013, Vol 31, Issue 6, p968
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000350115