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）段倾向于与脂质双层的疏水厚度相匹配，以最大程度地减少能量的不匹配并维持适当的蛋白质以进行功能。最近的数据表明，这种亲密的蛋白质/双层相互作用也与K+通道中的结构/功能相关。在这里，我们将阐明基本结构原理，这些原理与蛋白/脂质相互作用和通道功能的K+通道相关。该方法基于在不同脂质环境中模型K+通道KCV的活性。这种真正的最小通道KCV是一个合适的模型，因为它没有明显的细胞质结构域。因此，结构特性在很大程度上由TM段确定。此外，功能数据已经促进了以下假设：蛋白质/双层相互作用会影响KCV的关键特性，例如选择性和门控。本项目的重点是理解蛋白质/双层相互作用的外脂暴露的TM域的功能作用。该目标将通过重组和电气表征蛋白质和突变体在异源系统中以及不同厚度不同的平面脂质双层中具有改变的结构特性。