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Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K~+ channels

机译:去除膜脂的磷酸根基团可固定K〜+通道的电压传感器

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摘要

A fundamental question about the gating mechanism of voltage-activated K~+ (Kv) channels is how five positively charged voltage-sensing residues in the fourth transmembrane segment are energetically stabilized, because they operate in a low-dielectric cell membrane. The simplest solution would be to pair them with negative charges. However, too few negatively charged channel residues are positioned for such a role. Recent studies suggest that some of the channel's positively charged residues are exposed to cell membrane phospholipids and interact with their head groups. A key question nevertheless remains: is the phospho-head of membrane lipids necessary for the proper function of the voltage sensor itself? Here we show that a given type of Kv channel may interact with several species of phospholipid and that enzymatic removal of their phospho-head creates an insuperable energy barrier for the positively charged voltage sensor to move through the initial gating step(s), thus immobilizing it, and also raises the energy barrier for the downstream step(s).
机译:关于电压激活的K〜+(Kv)通道的门控机制的一个基本问题是,第四跨膜片段中的五个带正电的电压感应残基如何在能量上稳定,因为它们在低介电细胞膜中工作。最简单的解决方案是将它们与负电荷配对。但是,很少有带负电的通道残留物可以发挥这种作用。最近的研究表明,该通道的某些带正电荷的残基暴露于细胞膜磷脂中,并与它们的头基相互作用。但是,仍然存在一个关键问题:膜脂质的磷酸头对于电压传感器本身的正常功能是必需的吗?在这里,我们显示给定类型的Kv通道可能与几种磷脂相互作用,并且其磷头的酶促去除为正电荷电压传感器移动通过初始选通步骤创造了不可克服的能垒,从而实现了固定化并增加了下游步骤的能垒。

著录项

  • 来源
    《Nature》 |2008年第7180期|p.826-829|共4页
  • 作者单位
  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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