Inter-α/β subunits coupling mediating pre-inactivation and augmented activation of BKCa(β2).
Inter-α/β subunits coupling mediating pre-inactivation and augmented activation of BKCa(β2).
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DOI：
10.1038/srep01666
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发表时间：
2013
影响因子：
4.6
通讯作者：
Ding, Jiuping
中科院分区：
文献类型：
--
作者：
Hou, Panpan;Zeng, Wenping;Gan, Geliang;Lv, Caixia;Guo, Xiying;Zhang, Zheng;Liu, Haowen;Wu, Ying;Yao, Jing;Wei, Aguan D.;Wang, Sheng;Ding, Jiuping
大电导钙活化钾（BK）通道调节可兴奋细胞的电特性和神经递质释放。它的辅助β2亚基不仅增强门控，而且通过短暂的预失活状态使其失活。然而，β2增强和预失活BK通道的机制尚不清楚。利用我们新开发的方法，我们证明了静电力在形成α和β亚基之间的多个互补结合位点中起着至关重要的作用，包括通道预失活所需的“PI位点”，增强钙敏感性的“E位点”和“ECaB”偶联位点，通过β2(K33, R34, K35)， E位点和S6-C连接体将力从Ca2+-bowl传递到gate，独立于另一个Ca2+结合位点mSlo1（D362,D367）。在此基础上，构建了BK（β2）复合物的综合结构模型，为进一步了解其他BK（β）复合物激活和预失活的结构机制奠定了基础。
Large-conductance calcium-activated potassium (BK) channels regulate the electric properties and neurotransmitter release in excitable cells. Its auxiliary β2 subunits not only enhance gating, but also confer inactivation via a short-lived preinactivated state. However, the mechanism of enhancement and preinactivation of BK channels by β2 remains elusive. Using our newly developed methods, we demonstrated that electrostatic forces played a crucial role in forming multiple complementary pairs of binding sites between α and β subunits including a “PI site” required for channel preinactivation, an “E site” enhancing calcium sensitivity and an “ECaB” coupling site transferring force to gate from the Ca2+-bowl via the β2(K33, R34, K35), E site and S6-C linker, independent of another Ca2+ binding site mSlo1(D362,D367). A comprehensive structural model of the BK(β2) complex was reconstructed based on these functional studies, which paves the way for a clearer understanding of the structural mechanisms of activation and preinactivation of other BK(β) complexes.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
16.2
作者：
Quirk, JC;Reinhart, PH
通讯作者：
Reinhart, PH
影响因子：
3.7
作者：
Chen M;Gan G;Wu Y;Wang L;Wu Y;Ding J
通讯作者：
Ding J
影响因子：
64.5
作者：
CARTER, PJ;WINTER, G;FERSHT, AR
通讯作者：
FERSHT, AR
DOI：
10.1073/pnas.96.7.4137
发表时间：
1999-03-30
影响因子：
11.1
作者：
Wallner, M;Meera, P;Toro, L
通讯作者：
Toro, L