Contributions of counter-charge in a potassium channel voltage-sensor domain.
Contributions of counter-charge in a potassium channel voltage-sensor domain.
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DOI：
10.1038/nchembio.622
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发表时间：
2011-07-24
影响因子：
14.8
通讯作者：
Ahern CA
中科院分区：
文献类型：
--
作者：
Pless SA;Galpin JD;Niciforovic AP;Ahern CA
电压传感器域耦合膜电位的电压门控离子通道和磷酸酶的构象变化。高度共进化的酸性和芳香族侧链有助于阳离子侧链在电压感测期间跨越跨膜电场的转移。我们调查的功能贡献的负静电电位从这些残基通道门控和电压传感与非天然氨基酸诱变，电生理，电压钳荧光和从头计算。数据显示，在Shaker钾通道中跨膜段S2和S3中的两个保守酸性侧链Glu 293和Asp 316的中和对电导-电压关系几乎没有功能影响，尽管Glu 293似乎催化S4运动。我们的研究结果表明，无论是Glu 293还是Asp 316都不参与与S4的静电状态依赖性电荷-电荷相互作用，可能是因为它们占据并可能帮助创建充满水的前庭。
Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly co-evolved acidic and aromatic side-chains assist the transfer of cationic side-chains across the transmembrane electric field during voltage-sensing. We investigated the functional contribution of negative electrostatic potentials from these residues to channel gating and voltage-sensing with unnatural amino acid mutagenesis, electrophysiology, voltage-clamp fluorometry and ab initio calculations. The data show that neutralization of two conserved acidic side-chains in transmembrane segments S2 and S3, Glu293 and Asp316 in Shaker potassium channels, have little functional effect on conductance-voltage relationships, although Glu293 appears to catalyze S4 movement. Our results suggest that neither Glu293 nor Asp316 engages in electrostatic state-dependent charge-charge interactions with S4, likely because they occupy, and possibly help create, a water-filled vestibule.