Lipid bilayer properties and K+ channel function

膜蛋白的跨膜(TM)片段往往与脂双层的疏水厚度相匹配，以最大限度地减少能量的错配，并保持蛋白质的适当组织以发挥功能。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，我们将阐明与K+通道中蛋白质/脂类相互作用和通道功能相关的基本结构原理。该方法基于模型K+通道Kcv在不同脂质环境中的活性。这个真正最小的通道Kcv是一个合适的模型，因为它没有显著的细胞质结构域；因此结构特性在很大程度上由TM片段决定。此外，功能数据已经支持了这样的假设，即蛋白质/双层相互作用影响Kcv的关键属性，如选择性和门控。本项目特别关注于了解外层、脂质暴露的TM结构域在蛋白质/双层相互作用中的功能作用。这一目标将通过在异源体系和不同厚度的平面脂质双层中重组和电学表征结构性质改变的蛋白质和突变体来实现。

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.