Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel.
Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel.
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作者：
高电导 Ca2+ 门控 K+ (BK) 通道对于平滑肌收缩和神经递质释放等许多生物过程至关重要。这组通道可以被电压和细胞内 Ca2+ 协同激活，其中较大的 C 端细胞内部分负责 Ca2+ 感应。在这里，我们展示了游离 Ca2+ 状态下人 BK 通道整个细胞质区域的晶体结构。该结构揭示了四个细胞内亚基，每个亚基包含两个串联 RCK 结构域，组装成类似于 MthK 通道中所见的门环，并且可能代表其生理组装。根据诱变数据，将包括 Ca2+ 碗在内的三个 Ca2+ 结合位点映射到结构上。 Ca2+ 碗位于第二个 RCK 结构域内，形成 EF 手状基序，并战略性地定位在靠近两个亚基之间的组装界面处。另外两个 Ca2+（或 Mg2+）结合位点 Asp367 和 Glu374/Glu399 位于第一个 RCK 结构域上。 Asp367 位点具有高 Ca2+ 敏感性，位于 RCK1 N 端和 C 端子结构域之间的凹槽中，而低亲和力 Mg2+ 结合 Glu374/Glu399 位点位于门环的上平台并靠近膜。我们的结构还包含连接跨膜和细胞内域的连接体，使我们能够以合理的精度将已知结构的电压门控 K+ 通道孔对接到门环上，并生成完整 BK 通道的结构模型。
High-conductance Ca2+-gated K+ (BK) channels are essential for many biological processes such as smooth muscle contraction and neurotransmitter release. This group of channels can be activated synergistically by both voltage and intracellular Ca2+, with the large C-terminal intracellular portion being responsible for Ca2+ sensing. Here we present the crystal structure of the entire cytoplasmic region of the human BK channel in a Ca2+ free state. The structure reveals four intracellular subunits, each comprising two tandem RCK domains, assembled into a gating ring similar to that seen in the MthK channel and likely representing its physiological assembly. Three Ca2+ binding sites including the Ca2+ bowl are mapped onto the structure based on mutagenesis data. The Ca2+ bowl, located within the second RCK domain, forms an EF-hand like motif and is strategically positioned close to the assembly interface between two subunits. The other two Ca2+ (or Mg2+) binding sites, Asp367 and Glu374/Glu399, are located on the first RCK domain. The Asp367 site has high Ca2+ sensitivity and is positioned in the groove between the N- and C- terminal subdomains of RCK1, whereas the low affinity Mg2+-binding Glu374/Glu399 site is positioned on the upper plateau of the gating ring and close to the membrane. Our structure also contains the linker connecting the transmembrane and intracellular domains, allowing us to dock a voltage-gated K+ channel pore of known structure onto the gating ring with reasonable accuracy and generate a structural model for the full BK channel.
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影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
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：
16.8
作者：
Hou, Shangwei;Xu, Rong;Hoshi, Toshinori
通讯作者：
Hoshi, Toshinori
影响因子：
16.2
作者：
Jiang, YX;Pico, A;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1085/jgp.20028689
发表时间：
2002-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Lingle CJ
通讯作者：
Lingle CJ