Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin
Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin
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DOI：
10.1038/35074145
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发表时间：
2001-04-26
期刊：
影响因子：
64.8
通讯作者：
Adelman, JP
中科院分区：
文献类型：
--
作者：
Schumacher, MA;Rivard, AF;Adelman, JP
小电导Ca 2+激活的K+通道（SK通道）（1，2）不依赖于电压，仅由细胞内Ca 2+门控。这些膜通道是异聚体复合物，其包含孔形成α-亚基和Ca 2+结合蛋白钙调蛋白（CaM）。CaM通过CaM结合结构域（CaMBD）与SK通道结合，CaM结合结构域位于α亚基的胞内区域，紧邻孔的羧基末端（3，4）。当Ca 2+结合CaM4的N叶中的EF手时，触发通道开放。在这里，我们报告了SK通道CaMBD/Ca 2 +/CaM复合物的1.60埃晶体结构。CaMBD形成一个细长的二聚体，在每个末端结合一个CaM分子;每个CaM包裹三个α-螺旋，两个来自一个CaMBD亚基，一个来自另一个。由于只有钙调素N-叶结合钙离子，结构提供了钙依赖性和非依赖性钙调素/蛋白质相互作用的视图。结合生化数据，该结构表明SK通道可能存在门控机制。
Small-conductance Ca2+-activated K+ channels (SK channels)(1,2) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming a-subunits and the Ca2+-binding protein calmodulin (CaM). CaM binds to the SK channel through the CaM-binding domain (CaMBD), which is located in an intracellular region of the a-subunit immediately carboxy-terminal to the pore(3,4). Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of CaM4. Here we report the 1.60 Angstrom crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three alpha -helices, two from one CaMBD subunit and one from the other. As only the CaM N-lobe has bound Ca2+, the structure provides a view of both calcium-dependent and -independent CaM/protein interactions. Together with biochemical data, the structure suggests a possible gating mechanism for the SK channel.