Lipid bilayer properties and K+ channel function

脂质双层特性和 K 通道功能

• 批准号: 50950375
• 负责人: Professor Dr. Gerhard Thiel
• 金额: --
• 依托单位: Arbeitsgruppe Plant Membrane Biophysics
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/50950375?language=en
• 关键词: Lipid; bilayer; properties; K+; channel

Transmembrane (TM) segments of membrane proteins tend to match the hydrophobic thickness of the lipid bilayer to minimize mismatch of energy and to maintain a proper organization of the protein for function. Recent data suggest that this intimate protein/ bilayer interplay is also relevant for structure/function correlates in K+ channels. Here we shall elucidate fundamental structural principles, which are relevant in K+ channels for protein/lipid interactions and channel functions. The approach is based on the activity of the model K+ channel Kcv in different lipid environments. This truly minimal channel Kcv is a suitable model because it has no significant cytoplasmic domains; hence structural properties are largely determined by the TM segments. Furthermore functional data already foster the hypothesis that a protein/bilayer interaction affects key properties of Kcv such as selectivity and gating. The present project is focussed in particular on understanding the functional role of the outer, lipid exposed TM domain for protein/bilayer interplay. This goal will be achieved by reconstituting and electrically characterizing the protein and mutants with altered structural properties in heterologous systems and in planar lipid bilayers of different thickness.

膜蛋白的跨膜（TM）区段倾向于匹配脂双层的疏水厚度，以使能量的错配最小化并维持蛋白质的适当组织以用于功能。最近的数据表明，这种亲密的蛋白质/双层的相互作用也是相关的结构/功能相关的K+通道。在这里，我们将阐明基本的结构原理，这是相关的K+通道的蛋白质/脂质相互作用和通道功能。该方法是基于模型K+通道KCV在不同脂质环境中的活性。这种真正最小的通道Kcv是一个合适的模型，因为它没有显着的胞质结构域，因此结构特性主要由TM片段决定。此外，功能数据已经促进了蛋白质/双层相互作用影响Kcv的关键特性（如选择性和门控）的假设。本项目的重点是特别是了解的功能作用的外部，脂质暴露的TM结构域的蛋白质/双层相互作用。这一目标将通过重组和电特性的蛋白质和突变体在异源系统和不同厚度的平面脂质双层中的结构特性改变来实现。