LIPIDPROD - Lipid-protein interactions in membrane organisation

LIPIDPROD - 膜组织中的脂质-蛋白质相互作用

• 批准号: 128127235
• 负责人: Professorin Dr. Petra Schwille
• 金额: --
• 依托单位: Max-Planck-Institut für molekulare Zellbiologie und Genetik (MPI-CBG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/128127235?language=en
• 关键词: LIPIDPROD; Lipid; protein; interactions; membrane

Membranes are central to understand cellular organization and function. However, the lipid bilayer, which constitutes the fluid matrix of the membrane, was for years neglected and considered to be a mere solvent for the proteins associated with the membrane. This view changed with the increasing awareness of the complexity of the lipid composition of bilayers. Eukaryotic membrane lipids are glycerophospholipids, sphingolipids, and sterols and it is thought that more than 1,000 different lipid species are present in mammalian cells. Why there are so many lipids in cell membranes is not understood.Another promoter of bilayer research was the introduction of the lipid raft concept to subcompartmentalize cell membranes. This concept suggests that cell membranes containing sphingolipids, saturated phosphatidylcholine and cholesterol are occupied by fluctuating nanoscale assembles that are poised for coalescence into larger scale, more stable domains (including some and excluding other proteins) that are postulated to function for membrane trafficking and signaling.The objectives of this CRP are to understand:1. The spatial, nanoscopic, organization of both lipid-anchored and transmembrane proteins within membranes of live cells with special emphasis on proteins that have been claimed to be raft-associated.2. How these nanoscopic membrane protein assemblies can associate to generate more stable raft platforms with additional functions.3. How membrane proteins interact with the different lipid species and how lipid-protein interactions contribute to membrane function. One specific issue will be to analyze how transmembrane proteins become “raftophilic”.4. Studies in cells will be complemented by reconstitution studies of selected proteins using simplified model systems such as Giant Unilamelar Vesicles. The goal will be to find the lipid requirements for association with-raft domain.5. To develop methodology to simulate and model the interplay of lipids and proteins over a multitude of scales in time and space.

膜是理解细胞组织和功能的核心，然而，构成膜的流体基质的脂质双层多年来一直被忽视，并被认为仅仅是与膜相关的蛋白质的溶剂。随着人们对细胞膜的认识的不断深入，这种观点发生了变化。认识到双层脂质组成的复杂性，真核细胞膜脂质包括甘油磷脂、鞘脂和甾醇，并且认为哺乳动物细胞中存在 1,000 多种不同的脂质种类。为什么细胞膜中有如此多的脂质尚不清楚。双层研究的另一个推动者是引入脂筏概念来对细胞膜进行亚区室化。这一概念表明，含有鞘脂、饱和磷脂酰胆碱和胆固醇的细胞膜被波动的纳米级组装体占据。准备合并成更大规模、更稳定的结构域（包括一些蛋白质但排除其他蛋白质），这些结构域被假定为膜运输和信号传导发挥作用。该 CRP 旨在了解：1. 活细胞膜内脂质锚定蛋白和跨膜蛋白的空间、纳米级组织，特别强调那些声称与筏相关的蛋白质。2. 这些纳米级膜蛋白如何组装。可以结合产生具有附加功能的更稳定的筏平台。3.膜如何与不同的脂质种类相互作用以及脂质-蛋白质相互作用如何促进膜功能。 4. 细胞研究将通过使用简化的模型系统（例如巨型单层囊泡）进行重建研究来补充。5. 开发方法。在时间和空间的多个尺度上模拟和建模脂质和蛋白质的相互作用。