Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
T-6, MS K710, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
Sci Rep. 2017 Nov 30;7(1):16647. doi: 10.1038/s41598-017-16865-6.
Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies of an inwardly rectifying potassium (Kir) channel which forms specific interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP). The tendency of protein molecules to cluster has the effect of organizing the membrane into dynamic compartments. At the same time, the diversity of lipids present has a marked effect on the clustering behavior of ion channels. Sub-diffusion of proteins and lipids is observed. Protein crowding alters the sub-diffusive behavior of proteins and lipids such as PIP which interact tightly with Kir channels. Protein crowding also affects bilayer properties, such as membrane undulations and bending rigidity, in a PIP-dependent manner. This interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.
细胞膜是拥挤而复杂的环境。为了研究蛋白质-脂质相互作用对哺乳动物细胞膜动态组织的影响，我们进行了包含> 100 个内向整流钾（Kir）通道的粗粒度分子动力学模拟，该通道与调节脂质磷脂酰肌醇 4,5-二磷酸（PIP）形成特异性相互作用。蛋白质分子的聚集倾向于将膜组织成动态隔室。同时，存在的脂质多样性对离子通道的聚类行为有显著影响。观察到蛋白质和脂质的亚扩散。蛋白质拥挤改变了与 Kir 通道紧密相互作用的蛋白质和脂质（如 PIP）的亚扩散行为。蛋白质拥挤还以 PIP 依赖的方式影响双层性质，如膜波动和弯曲刚性。这种 Kir 通道扩散和动态组织之间的相互作用可能对通道功能具有重要意义。
