Structure of the TRPV1 ion channel determined by electron cryo-microscopy.
Structure of the TRPV1 ion channel determined by electron cryo-microscopy.
复制标题
作者：
瞬时受体电位（TRP）通道是多种细胞和环境信号的传感器，但由于缺乏详细的结构信息，阐明这些通道如何响应物理和化学刺激一直受到阻碍。在这里，我们利用电子冷冻显微镜的进步，以 3.4Å 的分辨率确定哺乳动物 TRP 通道 TRPV1 的结构，打破了膜蛋白无需结晶的侧链分辨率障碍。与电压门控通道一样，TRPV1 在由跨膜螺旋 S5-S6 和中间孔环形成的中心离子通路周围表现出四重对称性，该通路两侧是 S1-S4 电压传感器样域。 TRPV1 具有宽的细胞外“嘴”和短的选择性过滤器。保守的“TRP 结构域”与 S4-S5 连接子相互作用，与其对变构调节的贡献一致。细胞质结构域（包括 N 末端锚蛋白重复序列）之间的相互作用促进了亚基的组织。这些观察结果为理解 TRP 通道功能的独特方面提供了结构蓝图。
Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here, we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane helices S5–S6 and the intervening pore loop, which is flanked by S1–S4 voltage sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including N-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.
登录
查看更多内容
影响因子：
16.2
作者：
Cao E;Cordero-Morales JF;Liu B;Qin F;Julius D
通讯作者：
Julius D
影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
通讯作者：
Cheng, Yifan
影响因子：
2.9
作者：
Inada H;Procko E;Sotomayor M;Gaudet R
通讯作者：
Gaudet R