A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel
A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel
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DOI：
10.1016/s0896-6273(00)80904-6
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发表时间：
2000-02-01
期刊：
影响因子：
16.2
通讯作者：
Swartz, KJ
中科院分区：
文献类型：
--
作者：
Li-Smerin, YY;Hackos, DH;Swartz, KJ
电压门控性K+通道包含一个中心孔结构域和四个周围的电压敏感结构域。电压敏感域的结构变化如何以及在何处耦合到孔域，从而门控离子传导尚不清楚。KcsA是一种与电压门控K+通道孔结构域同源的细菌K+通道，其晶体结构为解决这一问题提供了一个起点。在这种结构的指导下，我们使用Shaker电压门控K+通道中孔结构域的跨膜壳上的Dahan扫描诱变来定位潜在的蛋白质-蛋白质和蛋白质-脂质界面。一些突变体仅引起门控的微小变化，并且当映射到远离孔结构域亚基之间的界面的KcsA结构簇上时。相比之下，突变体产生门控的大变化往往聚集在这个界面附近。这些结果意味着电压敏感域与邻近孔域亚基之间的界面附近的局部区域相互作用。
Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.