开放式人类以太网相关的K+通道的冷电磁结构hERG
Weiwei Wang1, Roderick MacKinnon1
1Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Cell
|April 22, 2017
概括
人类以太流通相关通道 (hERG) 的结构显示其脱极化,开放状态. 这种结构解释了hERG
科学领域:
- 分子生物学
- 心脏病学
- 结构生物学
背景情况:
- 人体以太与相关的通道 (hERG,Kv11.1) 对于心脏动作潜力的再极化至关重要.
- 与长QT综合征和torsade de pointes,一种可能致命的心律失常有关.
研究的目的:
- 确定hERG通道的分子结构.
- 阐明hERG通道功能和药物敏感性的结构基础.
主要方法:
- 使用冷电子显微镜以3.8 Å的分辨率解析hERG结构.
主要成果:
- 确定的结构显示hERG具有开放孔隙的脱极化形状.
- 一个独特的中腔与疏水口袋可能解释hERG的药物敏感性.
- 选择性过器的一个特殊特征可能与其快速停用有关.
结论:
- 高分辨率结构提供了前所未有的hERG通道门和功能.
- 了解hERG的结构对于开发更安全的药物和治疗心律失常至关重要.
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