Cryo-electron microscopy structure of the TRPV2 ion channel.
Cryo-electron microscopy structure of the TRPV2 ion channel.
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DOI：
10.1038/nsmb.3159
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发表时间：
2016-02
影响因子：
16.8
通讯作者：
Lee SY
中科院分区：
文献类型：
--
作者：
Zubcevic L;Herzik MA Jr;Chung BC;Liu Z;Lander GC;Lee SY
瞬时受体电位香草酸（TRPV）阳离子通道是参与多种生理过程的多模态传感器。TRPV 2是TRPV家族的一员，受温度、配体（如丙磺舒和大麻素）和脂质调节。TRPV2参与了许多生物学功能，包括躯体感觉、触觉感觉和先天免疫。在这里，我们提出了原子模型的兔TRPV2在其假定的脱敏状态，确定了冷冻EM在一个标称分辨率为4 μ m。在TRPV2结构中，参与门打开的跨膜区段6（S6）采用与在TRPV1中观察到的构象不同的构象。TRPV 1和TRPV 2的结构比较表明，锚蛋白重复结构域的旋转通过TRP结构域与孔开放偶联，并且这种孔开放可以通过S6二级结构的重排来调节。
Transient receptor potential vanilloid (TRPV) cation channels are polymodal sensors involved in a variety of physiological processes. TRPV2, a member of the TRPV family, is regulated by temperature, by ligands, such as probenecid and cannabinoids, and by lipids. TRPV2 has been implicated in many biological functions, including somatosensation, osmosensation and innate immunity. Here we present the atomic model of rabbit TRPV2 in its putative desensitized state, as determined by cryo-EM at a nominal resolution of ~4 Å. In the TRPV2 structure, the transmembrane segment 6 (S6), which is involved in gate opening, adopts a conformation different from the one observed in TRPV1. Structural comparisons of TRPV1 and TRPV2 indicate that a rotation of the ankyrin-repeat domain is coupled to pore opening via the TRP domain, and this pore opening can be modulated by rearrangements in the secondary structure of S6.