Lipid bilayer properties and K+ channel function

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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.