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

Cellular Physiology and Biochemistry

关键词: Ion channel;    Modulation;    Gating;    Conduction;    β-subunit;   

DOI  :  10.1159/000350115

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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 K_V1.5-Val481, K_V4.3-Leu368 and K_V7.1- 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 K_V 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.

【 授权许可】

CC BY-NC-ND