Lipid agonism: The PIP2 paradigm of ligand-gated ion channels.
Lipid agonism: The PIP2 paradigm of ligand-gated ion channels.
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DOI：
10.1016/j.bbalip.2015.01.011
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发表时间：
2015-05
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影响因子：
--
通讯作者：
Hansen SB
中科院分区：
文献类型：
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作者：
Hansen SB
在过去的十年中，膜信号脂成为离子通道功能的主要调节因子。然而，由于缺乏结构信息和定量和测量膜中脂质结合的分析，脂质与离子通道结合的分子性质仍然缺乏描述。脂质配体是如何与质膜中的膜蛋白结合的？脂质激活或调节离子通道意味着什么？脂质结合与可溶性神经递质激活如何比较？细胞是如何控制脂质激动作用的？本文综述了脂质及其与膜蛋白，特别是离子通道的相互作用。我讨论了膜脂生物学和离子通道生物物理学的交叉。膜脂是配体门控离子通道的真正激动剂。这些自由扩散的信号存在于质膜中，与蛋白质的跨膜结构域结合，并引起构象变化，从而变构地打开离子通道。该系统采用多种信号脂质的目录，最终由脂质酶和筏定位控制。我利用药理学、最近的蛋白质结构和电生理学数据来理解脂质调节，并将内向整流钾通道（Kir）定义为一类新的PIP2脂质门控离子通道。
The past decade, membrane signaling lipids emerged as major regulators of ion channel function. However, the molecular nature of lipid binding to ion channels remained poorly described due to a lack of structural information and assays to quantify and measure lipid binding in a membrane. How does a lipid-ligand bind to a membrane protein in the plasma membrane and what does it mean for a lipid to activate or regulate an ion channel? How does lipid-binding compare to activation by soluble neurotransmitter? And how does the cell control lipid agonism? This review focuses on lipids and their interactions with membrane proteins, in particular ion channels. I discuss the intersection of membrane lipid biology and ion channel biophysics. A picture emerges of membrane lipids as bona fide agonists of ligand-gated ion channels. These freely diffusing signals reside in the plasma membrane, bind to the transmembrane domain of protein, and cause a conformational change that allosterically gates an ion channel. The system employs a catalog of diverse signaling lipids ultimately controlled by lipid enzymes and raft localization. I draw upon pharmacology, recent protein structure, and electrophysiological data to understand lipid regulation and define inward rectifying potassium channels (Kir) as a new class of PIP2 lipid-gated ion channels.