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通过突变调节大电导钙激活钾通道的镁敏感性。

Tuning magnesium sensitivity of BK channels by mutations.

作者信息

Yang Huanghe, Hu Lei, Shi Jingyi, Cui Jianmin

机构信息

Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, Missouri 63130, USA.

出版信息

Biophys J. 2006 Oct 15;91(8):2892-900. doi: 10.1529/biophysj.106.090159. Epub 2006 Jul 28.

Abstract

Intracellular Mg(2+) at physiological concentrations activates mSlo1 BK channels by binding to a metal-binding site in the cytosolic domain. Previous studies suggest that residues E374, Q397, and E399 are important in Mg(2+) binding. In the present study, we show that mutations of E374 or E399 to other amino acids, except for Asp, abolish Mg(2+) sensitivity. These results further support that the side chains of E374 and E399 are essential for Mg(2+) coordination. To the contrary, none of the Q397 mutations abolishes Mg(2+) sensitivity, suggesting that its side chain may not coordinate to Mg(2+). However, because Q397 is spatially close to E374 and E399, its mutations affect the Mg(2+) sensitivity of channel gating by either reducing or increasing the Mg(2+) binding affinity. The pattern of mutational effects and the effect of chemical modification of Q397C indicate that Q397 is involved in the Mg(2+)-dependent activation of BK channels and that mutations of Q397 alter Mg(2+) sensitivity by affecting the conformation of the Mg(2+) binding site as well as by electrostatic interactions with the bound Mg(2+) ion.

摘要

生理浓度下的细胞内镁离子(Mg²⁺)通过与胞质结构域中的金属结合位点结合来激活mSlo1 BK通道。先前的研究表明,E374、Q397和E399残基在Mg²⁺结合中起重要作用。在本研究中,我们发现将E374或E399突变为除天冬氨酸以外的其他氨基酸会消除Mg²⁺敏感性。这些结果进一步支持E374和E399的侧链对于Mg²⁺配位至关重要。相反,Q397的突变均未消除Mg²⁺敏感性,这表明其侧链可能不与Mg²⁺配位。然而,由于Q397在空间上靠近E374和E399,其突变通过降低或增加Mg²⁺结合亲和力来影响通道门控的Mg²⁺敏感性。突变效应模式以及Q397C的化学修饰效应表明,Q397参与BK通道的Mg²⁺依赖性激活,并且Q397的突变通过影响Mg²⁺结合位点的构象以及与结合的Mg²⁺离子的静电相互作用来改变Mg²⁺敏感性。

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本文引用的文献

1
Effects of multiple metal binding sites on calcium and magnesium-dependent activation of BK channels.
J Gen Physiol. 2006 Jan;127(1):35-49. doi: 10.1085/jgp.200509317. Epub 2005 Dec 12.
2
Homology modeling identifies C-terminal residues that contribute to the Ca2+ sensitivity of a BKCa channel.
Biophys J. 2005 Nov;89(5):3079-92. doi: 10.1529/biophysj.105.063610. Epub 2005 Aug 12.
4
Mapping the BKCa channel's "Ca2+ bowl": side-chains essential for Ca2+ sensing.
J Gen Physiol. 2004 May;123(5):475-89. doi: 10.1085/jgp.200409052.
5
The large-conductance Ca2+-activated K+ channel is essential for innate immunity.
Nature. 2004 Feb 26;427(6977):853-8. doi: 10.1038/nature02356.
8
Principles governing Mg, Ca, and Zn binding and selectivity in proteins.
Chem Rev. 2003 Mar;103(3):773-88. doi: 10.1021/cr020467n.
9
Gating mechanism of BK (Slo1) channels: so near, yet so far.
J Gen Physiol. 2003 Feb;121(2):81-96. doi: 10.1085/jgp.20028721.

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