在接近原子分辨率的子瑞诺丁受体 RyR1 的结构
Zhen Yan1,2,3, Xiaochen Bai4, Chuangye Yan2,3
1State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
Nature
|December 18, 2014
概括
这项研究揭示了赖诺丁受体 (RyRs) 的详细结构,这是肌肉收缩中的关键通道. 这为它们的高离子导电性和全调节机制提供了洞察力.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 分子生理学分子生理学
背景情况:
- 瑞诺丁受体 (RyRs) 是重要的高导电性细胞内Ca2+通道.
- 它们对于骨和心脏肌肉的激发-收缩合至关重要.
- RyRs是已知的最大的离子通道,具有同位四度结构.
研究的目的:
- 为了确定子RyR1通道的高分辨率结构.
- 阐明 RyR1 的功能和调节的结构基础.
- 了解 RyR1 与其调制器 FKBP12.12 之间的相互作用.
主要方法:
- 使用单粒子电子冷显微镜 (cryo-EM) 进行了研究.
- 确定了与FKBP12复合的子RyR1的结构.
- 进行了高分辨率 (3.8 Å) 的结构分析.
主要成果:
- 确定了三种新领域 (中央,手柄,螺旋) 带有 armadillo 重复折叠.
- 通道域共享电压离子通道折叠,但具有独特的特征.
- 一个带电的发针环和S6段形成孔隙,解释了高导电性和全调节.
结论:
- 确定的结构揭示了RyR1.1.的分子结构.
- 结构洞察力解释了高离子流量和RyR活动的长距离全控制.
- 这项工作为了解RyR通道病变和药物开发提供了基础.
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