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反电荷在钾通道电压传感器域中的作用。

Contributions of counter-charge in a potassium channel voltage-sensor domain.

机构信息

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

Nat Chem Biol. 2011 Jul 24;7(9):617-23. doi: 10.1038/nchembio.622.

DOI:10.1038/nchembio.622
PMID:21785425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4933587/
Abstract

Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly coevolved 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, namely Glu293 and Asp316 in Shaker potassium channels, has 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.

摘要

电压传感器结构域将膜电位与电压门控离子通道和磷酸酶的构象变化偶联。高度共进化的酸性和芳香族侧链有助于在电压感应过程中阳离子侧链穿过跨膜电场的转移。我们通过非天然氨基酸诱变、电生理学、电压钳荧光法和从头计算研究了这些残基的负静电势对通道门控和电压感应的功能贡献。数据表明,Shaker 钾通道跨膜片段 S2 和 S3 中两个保守酸性侧链(即 Glu293 和 Asp316)的中和对电导-电压关系几乎没有功能影响,尽管 Glu293 似乎催化 S4 运动。我们的结果表明,Glu293 和 Asp316 都不会与 S4 发生静电状态依赖的电荷-电荷相互作用,这可能是因为它们占据了可能有助于其形成的充满水的前庭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/37cdf4046534/nihms3964f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/ef0cfb3295e0/nihms3964f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/a5de5f1369ff/nihms3964f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/aef8b8be0a2d/nihms3964f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/700a4e61b6d0/nihms3964f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/37cdf4046534/nihms3964f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/ef0cfb3295e0/nihms3964f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/a5de5f1369ff/nihms3964f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/aef8b8be0a2d/nihms3964f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/700a4e61b6d0/nihms3964f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de70/4933587/37cdf4046534/nihms3964f5.jpg

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