The Mechanism of Membrane Fusion and Lipid Flip/Flop Explored with Model Transmembrane Helices

用跨膜螺旋模型探索膜融合和脂质翻转/翻转的机制

• 批准号: 260432530
• 负责人: Professor Dr. Dieter Langosch
• 金额: --
• 依托单位: Lehrstuhl Bionanotechnologie und Bioelektronik (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/260432530?language=en
• 关键词: Mechanism; Membrane; Fusion; Lipid; Flip

A diversity of biological processes, like membrane fusion and lipid flip/flop across membranes, are based on protein/lipid interactions. In previous work, we have developed low-complexity models - the LV-peptides - of transmembrane helices. These peptides catalyze membrane fusion and lipid flip. These functional properties depend on the backbone dynamics of the helices and the charge state of the flanking residues. In this proposal, we present testable hypotheses as to how the functional and the structural properties could be connected. We will examine these hypotheses using complementary experimental approaches and simulations in order to clarify the mechanism of membrane fusion and lipid flip. In particular, we will examine the capacity of a range of LV-helices to interact with chemically distinct lipids. First, these TMD/lipid interaction could cause lipid splay and thereby initiate membrane fusion. Second, we will assess whether the covalent stabilization of these interactions facilitates lipid flip, which would support the idea that PC lipids flip within disordered membrane domains. Third, we will test a new concept where flip of PE lipids is enabled by a coupled membrane translocation of TM helix and lipids.

生物过程的多样性，如膜融合和跨膜脂质翻转/翻转，是基于蛋白质/脂质相互作用。在以前的工作中，我们已经开发了低复杂性的模型-LV-肽-的跨膜螺旋。这些肽催化膜融合和脂质翻转。这些功能特性取决于螺旋的骨架动力学和侧翼残基的电荷状态。在这个建议中，我们提出了可检验的假设，以如何连接的功能和结构特性。我们将使用互补的实验方法和模拟来研究这些假设，以澄清膜融合和脂质翻转的机制。特别是，我们将研究一系列LV-螺旋与化学上不同的脂质相互作用的能力。首先，这些TMD/脂质相互作用可引起脂质张开，从而启动膜融合。其次，我们将评估这些相互作用的共价稳定是否有利于脂质翻转，这将支持PC脂质翻转无序膜结构域内的想法。第三，我们将测试一个新的概念，其中PE脂质的翻转是通过TM螺旋和脂质的偶联膜易位实现的。