Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel.
Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel.
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DOI：
10.1016/j.str.2016.07.020
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发表时间：
2016-10-04
期刊：
影响因子：
5.7
通讯作者：
Morais-Cabral, Joao Henrique
中科院分区：
文献类型：
--
作者：
Marques-Carvalho, Maria Joao;Oppermann, Johannes;Munoz, Eva;Fernandes, Andreia S.;Gabant, Guillaume;Cadene, Martine;Heinemann, Stefan H.;Schoenherr, Roland;Morais-Cabral, Joao Henrique
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The human EAG1 potassium channel belongs to the superfamily of KCNH voltage-gated potassium channels that have roles in cardiac repolarization and neuronal excitability. EAG1 is strongly inhibited by Ca2+-calmodulin (CaM) through a mechanism that is not understood. We determined the binding properties of CaM with each one of three previously identified binding sites (BDN, BDC1 and BDC2), analyzed binding to protein stretches that include more than one site, and determined the effect of neighboring globular domains on the binding properties. The determination of the crystal structure of CaM bound to BDC2 shows the channel fragment interacting with only the C-lobe of calmodulin and adopting an unusual bent conformation. Based on this structure and on a functional and biochemical analysis of mutants, we propose a model for the mechanism of inhibition where the local conformational change induced by CaM binding at BDC2 is at the basis of channel modulation.
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影响因子：
5.6
作者：
Marques-Carvalho, Maria J.;Sahoo, Nirakar;Morais-Cabral, Joao H.
通讯作者：
Morais-Cabral, Joao H.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Liu, Yanshun;Zheng, Xunhai;Birnbaumer, Lutz
通讯作者：
Birnbaumer, Lutz
DOI：
10.1085/jgp.201010582
发表时间：
2011-03
期刊：
The Journal of general physiology
影响因子：
--
作者：
Gustina AS;Trudeau MC
通讯作者：
Trudeau MC
影响因子：
3.3
作者：
Cherubini, A;Hofmann, G;Arcangeli, A
通讯作者：
Arcangeli, A