人类HCN1高极化激活通道的结构
Chia-Hsueh Lee1, Roderick MacKinnon1
1Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Cell
|January 14, 2017
概括
我们揭示了HCN通道的结构, 这些结构解释了独特的离子选择性以及循环AMP (cAMP) 如何控制心率调节的通道门.
科学领域:
- 生物物理
- 分子生物学
- 结构生物学
背景情况:
- 超极化激活的循环核酸门 (HCN) 通道调节心脏和神经节律器细胞的节律活动.
- HCN通道表现出电压依赖的逆极性,由细胞内循环腺单酸盐 (cAMP) 调节.
研究的目的:
- 确定人类HCN通道的高分辨率结构.
- 阐明独特的离子选择性,反向电压门和cAMP介导调节的机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得人体HCN通道的结构.
- 在3.5 Å分辨率下,在没有和存在cAMP的情况下确定结构.
主要成果:
- 这些结构显示出一种独特的K+通道选择性过器形成序列,负责Na+和K+的透性.
- 电压传感器处于无极化形状,孔口关闭,具有延伸的S4螺旋,封闭孔口.
- cAMP结合会诱导细胞质域的结构变化,促进孔隙的开放.
结论:
- 这些结构为HCN通道功能提供了前所未有的洞察力.
- 这些发现有助于了解离子选择性,反向极性以及cAMP在调节心脏和神经节律中的作用.
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