文章基本信息

标题：PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6
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作者：Marina A. Kasimova ; Mark A. Zaydman ; Jianmin Cui 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep07474
出版社：Springer Nature
摘要：Among critical aspects of voltage-gated potassium (Kv) channels' functioning is the effective communication between their two composing domains, the voltage sensor (VSD) and the pore. This communication, called coupling, might be transmitted directly through interactions between these domains and, as recently proposed, indirectly through interactions with phosphatidylinositol-4,5-bisphosphate (PIP₂), a minor lipid of the inner plasma membrane leaflet. Here, we show how the two components of coupling, mediated by protein-protein or protein-lipid interactions, both contribute in the Kv7.1 functioning. On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP₂ binding site that involves residues playing a key role in PIP₂-dependent coupling. On the other hand, combined theoretical and experimental approaches have shown that the direct interaction between the segments of the VSD (S4–S5) and the pore (S6) is weakened by electrostatic repulsion. Finally, we conclude that due to weakened protein-protein interactions, the PIP₂-dependent coupling is especially prominent in Kv7.1.