The molecular architecture of dihydropyrindine receptor/L-type Ca2+ channel complex
The molecular architecture of dihydropyrindine receptor/L-type Ca2+ channel complex
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DOI：
10.1038/srep08370
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发表时间：
2015-02-10
影响因子：
4.6
通讯作者：
Yin, Chang-Cheng
中科院分区：
文献类型：
--
作者：
Hu, Hongli;Wang, Zhao;Yin, Chang-Cheng
二氢吡啶受体（DHPR）是一种L型钙通道复合物，在肌肉收缩、分泌、神经元突触输入整合和突触传递中起重要作用。DHPR复合物的分子结构仍然难以捉摸。在这里，我们提出了一个15埃分辨率的骨骼DHPR/L型钙通道复合物的冷冻电子显微镜结构。DHPR具有通过钩状延伸部连接的不对称主体。主体由“梯形”和“四面体”组成。同源物晶体结构对接和位点特异性抗体标记显示，α 1和α 2亚基位于“梯形”，β亚基位于“四面体”。该结构揭示了真核细胞Ca 2+通道复合物的分子结构。此外，这种结构提供了结构上的见解DHPR参与与RyR/Ca 2+释放通道的物理耦合的关键要素，并阐明了兴奋-收缩耦合的机制。
Dihydropyridine receptor (DHPR), an L-type Ca2+ channel complex, plays an essential role in muscle contraction, secretion, integration of synaptic input in neurons and synaptic transmission. The molecular architecture of DHPR complex remains elusive. Here we present a 15-angstrom resolution cryo-electron microscopy structure of the skeletal DHPR/L-type Ca2+ channel complex. The DHPR has an asymmetrical main body joined by a hook-like extension. The main body is composed of a "trapezoid" and a "tetrahedroid". Homologous crystal structure docking and site-specific antibody labelling revealed that the alpha 1 and alpha 2 subunits are located in the "trapezoid" and the beta subunit is located in the "tetrahedroid". This structure revealed the molecular architecture of a eukaryotic Ca2+ channel complex. Furthermore, this structure provides structural insights into the key elements of DHPR involved in physical coupling with the RyR/Ca2+ release channel and shed light onto the mechanism of excitation-contraction coupling.