Lipids in the structure, folding, and function of the KcsA K+ channel
Lipids in the structure, folding, and function of the KcsA K+ channel
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DOI：
10.1021/bi026215y
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发表时间：
2002-09-03
期刊：
影响因子：
2.9
通讯作者：
Mackinnon, R
中科院分区：
文献类型：
--
作者：
Valiyaveetil, FI;Zhou, YF;Mackinnon, R
脂质分子在细胞膜的天然环境中包围离子通道。脂双层的重要性和脂蛋白相互作用在离子通道结构和功能中的作用还没有得到很好的理解。在这里，我们证明了细菌钾通道KcsA结合带负电荷的脂质分子。我们已经定义了潜在的结合位点的脂质分子上KcsA的KcsA的复合物与单克隆抗体Fab片段的X-射线晶体学分析。我们还表明，脂质是所需的KcsA四聚体从未折叠的单体状态的体外重折叠。KcsA四聚体的正确重折叠需要脂质，但它不依赖于带负电荷的脂质，因为重折叠在不存在此类脂质的情况下发生。我们确认，带负电荷的脂质的存在下，需要通过KcsA钾离子通道的离子传导，这表明结合到KcsA的脂质是重要的离子通道功能。
Lipid molecules surround an ion channel in its native environment of cellular membranes. The importance of the lipid bilayer and the role of lipid protein interactions in ion channel structure and function are not well understood. Here we demonstrate that the bacterial potassium channel KcsA binds a negatively charged lipid molecule. We have defined the potential binding site of the lipid molecule on KcsA by X-ray crystallographic analysis of a complex of KcsA with a monoclonal antibody Fab fragment. We also demonstrate that lipids are required for the in vitro refolding of the KcsA tetramer from the unfolded monomeric state. The correct refolding of the KcsA tetramer requires lipids, but it is not dependent on negatively charged lipids as refolding takes place in the absence of such lipids. We confirm that the presence of negatively charged lipids is required for ion conduction through the KcsA potassium channel, suggesting that the lipid bound to KcsA is important for ion channel function.