Structural determinants of protein partitioning into ordered membrane domains and lipid rafts
Structural determinants of protein partitioning into ordered membrane domains and lipid rafts
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DOI：
10.1016/j.chemphyslip.2015.07.022
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发表时间：
2015-11-01
影响因子：
3.4
通讯作者：
Levental, Ilya
中科院分区：
文献类型：
--
作者：
Lorent, Joseph Helmuth;Levental, Ilya
越来越多的证据支持存在于质膜的横向纳米脂质结构域，称为脂筏。这些结构域优先募集膜蛋白和脂质以促进它们的相互作用，从而调节跨膜信号传导和细胞内稳态。筏结构域的功能本质上取决于其对特定膜组分的选择性;然而，虽然筏协会脂质的物理化学决定因素是已知的，但很少有系统的研究集中在指导筏蛋白质分配的结构方面。在这篇综述中，我们描述了生物物理和热力学方面的筏模拟液体有序相，专注于那些最相关的蛋白质分配。此外，我们详细介绍了用于研究蛋白质筏相互作用的各种实验模型。最后，我们回顾了现有的文献筏靶向机制，包括脂质翻译后修饰，脂质结合，跨膜结构域的功能。我们的结论是，虽然蛋白质棕榈酰化是一个明确的筏靶向信号，筏分区很少有其他一般的结构决定因素已被发现，这表明许多发现在这个新兴的领域。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Increasing evidence supports the existence of lateral nanoscopic lipid domains in plasma membranes, known as lipid rafts. These domains preferentially recruit membrane proteins and lipids to facilitate their interactions and thereby regulate transmembrane signaling and cellular homeostasis. The functionality of raft domains is intrinsically dependent on their selectivity for specific membrane components; however, while the physicochemical determinants of raft association for lipids are known, very few systematic studies have focused on the structural aspects that guide raft partitioning of proteins. In this review, we describe biophysical and thermodynamic aspects of raft-mimetic liquid ordered phases, focusing on those most relevant for protein partitioning. Further, we detail the variety of experimental models used to study protein-raft interactions. Finally, we review the existing literature on mechanisms for raft targeting, including lipid post-translational modifications, lipid binding, and transmembrane domain features. We conclude that while protein palmitoylation is a clear raft-targeting signal, few other general structural determinants for raft partitioning have been revealed, suggesting that many discoveries lie ahead in this burgeoning field. (C) 2015 Elsevier Ireland Ltd. All rights reserved.