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hERG 钾通道 S4-S5 连接环的溶液结构。

The solution structure of the S4-S5 linker of the hERG potassium channel.

机构信息

Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), Singapore 138669, Singapore.

出版信息

J Pept Sci. 2012 Feb;18(2):140-5. doi: 10.1002/psc.1427. Epub 2011 Nov 3.

DOI:10.1002/psc.1427
PMID:22052838
Abstract

The human ether-à-go-go related gene (hERG) encodes a protein that forms a voltage-gated potassium channel and plays an important role in the heart by controlling the rapid delayed rectifier K(+) current (I(Kr)). The S4-S5 linker was shown to be important for the gating of the hERG channel. Nuclear magnetic resonance study showed that a peptide derived from the S4-S5 linker had no well-ordered structure in aqueous solution and adopted a 3(10) -helix (E544-Y545-G546) structure in detergent micelles. The existence of an amphipathic helix was confirmed, which may be important for interaction with cell membrane. Close contact between side chains of residues R541 and E544 was observed, which may be important for its regulation of channel gating.

摘要

人类 ether-à-go-go 相关基因 (hERG) 编码一种形成电压门控钾通道的蛋白质,通过控制快速延迟整流钾电流 (I(Kr)) 在心脏中发挥重要作用。S4-S5 连接子被证明对 hERG 通道的门控很重要。核磁共振研究表明,源自 S4-S5 连接子的肽在水溶液中没有有序结构,并且在去污剂胶束中采用 3(10)-螺旋 (E544-Y545-G546) 结构。确认存在一个两亲螺旋,这可能对与细胞膜的相互作用很重要。观察到残基 R541 和 E544 的侧链之间的紧密接触,这可能对其调节通道门控很重要。

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