Caveolin induced membrane curvature and lipid clustering: two sides of the same coin?
Caveolin induced membrane curvature and lipid clustering: two sides of the same coin?
复制标题
Caveolin 诱导的膜曲率和脂质聚集：同一枚硬币的两面？
DOI：
10.1039/d0fd00062k
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发表时间：
2020
影响因子：
3.4
通讯作者：
Durba Sengupta
中科院分区：
文献类型：
--
作者：
Shikha Prakash;A. Krishna;Durba Sengupta
小窝蛋白1（Caveolin-1，cav-1）是一种多结构域的膜蛋白，在细胞信号转导、内吞作用和机械保护中起关键作用。它是富含胆固醇的小窝结构域的主要成分，据报道可诱导膜弯曲。cav-1与复杂膜相互作用的分子机制，导致膜拓扑结构的调节和富含胆固醇的结构域的形成，仍然难以捉摸。在这项研究中，我们的目的是了解脂质组成的影响，通过分析cav-1与复杂的膜双层组成的约60种脂质的相互作用。我们已经进行了一系列的粗粒分子动力学模拟，使用马提尼力场与cav-1蛋白质结构（残基82-136），包括膜结合结构域和棕榈酰尾巴。我们观察到cav-1在这个复杂的膜中诱导曲率，尽管它被限制在纳米长度尺度。同时，我们观察到胆固醇、鞘脂和其他脂质分子的聚集，导致纳米结构域的形成。直接微秒时间尺度的相互作用，观察到特定的脂质，如胆固醇，磷脂酰丝氨酸和磷脂酰乙醇胺脂质类型。结果表明，膜拓扑结构和脂质种类之间存在相互作用。我们的工作是一个步骤，了解脂质成分和组织如何调节小窝的形成，在内吞作用和细胞信号传导的背景下。
Caveolin-1 (cav-1) is a multi-domain membrane protein that is a key player in cell signaling, endocytosis and mechanoprotection. It is the principle component of cholesterol-rich caveolar domains and has been reported to induce membrane curvature. The molecular mechanisms underlying the interactions of cav-1 with complex membranes, leading to modulation of membrane topology and the formation of cholesterol-rich domains, remain elusive. In this study, we aim to understand the effect of lipid composition by analyzing the interactions of cav-1 with complex membrane bilayers comprised of about sixty lipid types. We have performed a series of coarse-grain molecular dynamics simulations using the Martini force-field with a cav-1 protein construct (residue 82-136) that includes the membrane binding domains and a palmitoyl tail. We observe that cav-1 induces curvature in this complex membrane, though it is restricted to a nanometer length scale. Concurrently, we observe a clustering of cholesterol, sphingolipids and other lipid molecules leading to the formation of nanodomains. Direct microsecond timescale interactions are observed for specific lipids such as cholesterol, phosphatidylserine and phosphatidylethanolamine lipid types. The results indicate that there is an interplay between membrane topology and lipid species. Our work is a step toward understanding how lipid composition and organization regulate the formation of caveolae, in the context of endocytosis and cell signaling.