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

Article

关键词: HIGH-LEVEL EXPRESSION;    CRYSTAL-STRUCTURE;    VOLTAGE;    PORE;    RECEPTOR;    VISUALIZATION;    SELECTIVITY;    MUTATIONS;    REVEALS;    SYSTEM;   

DOI  :  10.1038/nature12822

来源: SCIE

【 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.

【 授权许可】

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