Regulation of membrane protein structure and function by their lipid nano-environment.
Regulation of membrane protein structure and function by their lipid nano-environment.
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DOI：
10.1038/s41580-022-00524-4
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发表时间：
2023-03
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--
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跨膜蛋白占哺乳动物蛋白质组的约30%，介导代谢、信号传导、运输和细胞生命所需的许多其他功能。整合膜蛋白（IMP）的微环境本质上不同于细胞质，IMP被组成和生物代谢复杂的脂质基质溶剂化。这些溶剂化脂质以多种方式影响蛋白质结构和功能，从立体特异性、高亲和力蛋白质-脂质相互作用到通过本体膜性质进行调节。已经报道了各种转运蛋白、通道和信号受体通过其溶剂化膜对IMP进行功能调节的具体实例;然而，通过脂质环境调节IMP的可概括的机制原理既没有得到广泛理解，也没有完全理解。在这里，我们回顾了最近的见解复杂的哺乳动物脂质体，膜的理化性质产生的脂质集体之间的相互关系，和IMPs的监管之一或两者。最近增殖的高分辨率的方法来研究这种脂质-蛋白质相互作用，导致了概括的见解，这是合成到一个一般的框架称为“功能parabolidome”，了解膜蛋白和它们周围的脂质微环境之间的相互调节。
Transmembrane proteins comprise ~30% of the mammalian proteome, mediating metabolism, signaling, transport, and many other functions required for cellular life. The microenvironment of integral membrane proteins (IMPs) is intrinsically different from cytoplasmic ones, with IMPs solvated by a compositionally and biophysically complex lipid matrix. These solvating lipids affect protein structure and function in a variety of ways, from stereospecific, high-affinity protein-lipid interactions to modulation by bulk membrane properties. Specific examples of functional modulation of IMPs by their solvating membranes have been reported for various transporters, channels, and signal receptors; however, generalizable mechanistic principles governing IMP regulation by lipid environments are neither widely appreciated nor completely understood. Here, we review recent insights into the inter-relationships between complex mammalian lipidomes, the membrane physicochemical properties resulting from such lipid collectives, and the regulation of IMPs by either or both. The recent proliferation of high-resolution methods to study such lipid-protein interactions has led to generalizable insights, which are synthesized into a general framework termed the “functional paralipidome” for understanding the mutual regulation between membrane proteins and their surrounding lipid microenvironments.
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