Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation.
Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation.
复制标题
PIP2 脂质在电压门控钾通道表面的迁移影响通道失活
DOI：
10.1038/srep15079
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发表时间：
2015-10-15
影响因子：
4.6
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Chen L;Zhang Q;Qiu Y;Li Z;Chen Z;Jiang H;Li Y;Yang H
已发表的脂质-蛋白质相互作用的研究主要集中在脂质与蛋白质的单个位点的结合。在这里，我们证明脂质可以在蛋白质的不同结合位点之间迁移，并且这种迁移调节蛋白质功能。电压门控钾 (Kv) 通道有几个潜在的 4,5-二磷酸磷脂酰肌醇 (PIP2) 结合位点。我们对 KCNQ2 通道的分子动力学 (MD) 模拟表明，当通道处于开放状态时，PIP2 优先与 S4-S5 连接子结合，同时保持一定的迁移到 S2-S3 连接子的概率。在 MD 结果的指导下，使用 KCNQ2、KCNQ1 和 hERG 通道的电生理学实验表明，PIP2 向 S2-S3 连接子的迁移控制着通道的失活速率。数据表明，PIP2 可以在 Kv 通道的不同结合位点之间迁移，对通道失活产生重大影响，为脂质-蛋白质相互作用的动力学和生理功能提供新的见解。
Published studies of lipid-protein interactions have mainly focused on lipid binding to an individual site of the protein. Here, we show that a lipid can migrate between different binding sites in a protein and this migration modulates protein function. Voltage-gated potassium (Kv) channels have several potential binding sites for phosphatidylinositol-4,5-bisphosphate (PIP2). Our molecular dynamics (MD) simulations on the KCNQ2 channel reveal that PIP2 preferentially binds to the S4-S5 linker when the channel is in the open state while maintains a certain probability of migrating to the S2-S3 linker. Guided by the MD results, electrophysiological experiments using KCNQ2, KCNQ1 and hERG channels show that the migration of PIP2 toward the S2-S3 linker controls the deactivation rate of the channel. The data suggest that PIP2 can migrate between different binding sites in Kv channels with significant impacts on channel deactivation, casting new insights into the dynamics and physiological functions of lipid-protein interactions.