How highly charged anionic lipids bind and regulate ion channels.

How highly charged anionic lipids bind and regulate ion channels.
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DOI:
10.1085/jgp.200709936
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发表时间:
2008-05
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Baukrowitz T
Baukrowitz T
中科院分区:
其他
文献类型:
--
作者:
Tucker SJ;Baukrowitz T

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通过与膜脂的直接相互作用来调节离子通道活性是离子通道生物学中一个新兴的主题。特别是磷酸肌醇,如磷脂酰肌醇4,5 -二磷酸(PIP 2),已知可调节大多数主要类型的离子通道的活性,以及许多其他膜运输蛋白。PIP 2对内整流(Kir)钾通道的调节是研究通道-脂质相互作用最深入和定义最好的模型系统之一。在这篇综述中,我们探讨了磷酸肌苷和其他高电荷阴离子脂质(如长链辅酶a酯)对Kir通道复杂调节的机制。有趣的是,这些不同的脂质导致激活或抑制取决于Kir通道亚型。我们描述了最近的研究如何提供这些脂质诱导的门控运动的结构见解,并讨论了这种门控机制如何成为Kir通道生理学的核心。
The modulation of channel activity by direct interaction with membrane lipids is now an emerging theme in ion channel biology. In particular, phosphoinositides such as phosphatidylinositol 4, 5-bisphosphate (PIP 2) are known to regulate the activity of most major classes of ion channel, as well as a number of other membrane transport proteins. The regulation of inwardly rectifying (Kir) potassium channels by PIP 2 is one of the most intensively studied and best-defined model systems for studying channel–lipid interactions. In this review we explore the mechanisms that underlie the complex regulation of Kir channels by phosphoinositides and other highly charged anionic lipids such as long chain CoA esters. Intriguingly, these different lipids result in either activation or inhibition depending on the Kir channel subtype. We describe how recent studies have provided structural insight into these lipid-induced gating movements, and discuss how this gating mechanism is central to Kir channel physiology.
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