Structure of the TRPV1 ion channel determined by electron cryo-microscopy

被引:1283
作者
Liao, Maofu [1 ]
Cao, Erhu [2 ]
Julius, David [2 ]
Cheng, Yifan [1 ]
机构
[1] Univ Calif San Francisco, Dept Biochem & Biophys, Keck Adv Microscopy Lab, San Francisco, CA 94158 USA
[2] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
HIGH-LEVEL EXPRESSION; CRYSTAL-STRUCTURE; VOLTAGE; PORE; RECEPTOR; VISUALIZATION; SELECTIVITY; MUTATIONS; REVEALS; SYSTEM;
D O I
10.1038/nature12822
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 3.4 angstrom 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 segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a 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 amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.
引用
收藏
页码:107 / +
页数:18
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