Structures of TRPV2 in distinct conformations provide insight into role of the pore turret
Structures of TRPV2 in distinct conformations provide insight into role of the pore turret
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DOI：
10.1038/s41594-018-0168-8
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发表时间：
2019-01-01
影响因子：
16.8
通讯作者：
Wensel, Theodore G.
中科院分区：
文献类型：
--
作者：
Dosey, Timothy L.;Wang, Zhao;Wensel, Theodore G.
瞬时受体电位(Trp)家族的阳离子通道在调节其下门或上门的各种细胞内外刺激的刺激下开放，从而发挥重要的生理作用。尽管进行了广泛的研究，但耦合这些门的机制仍然不清楚。以前的结构未能解决细胞外环，在TRPV亚家族中被称为‘孔塔’，它是靠近上闸门的。我们通过活性分析和解决大鼠TRPV2的结构，分别在4.0埃和3.6埃的分辨率下有和没有完整的炮塔，确定了孔炮塔的重要性。这些结构分解了全长的毛孔转塔，揭示了TRPV2的完全开放和部分开放状态，两者都有空置的香草状口袋。我们的结果提示了一种机制，通过这种机制，生理信号，如脂质结合，可以调节下门，并通过孔塔促进的机制耦合到上门。
Cation channels of the transient receptor potential (TRP) family serve important physiological roles by opening in response to diverse intra- and extracellular stimuli that regulate their lower or upper gates. Despite extensive studies, the mechanism coupling these gates has remained obscure. Previous structures have failed to resolve extracellular loops, known in the TRPV subfamily as 'pore turrets', which are proximal to the upper gates. We established the importance of the pore turret through activity assays and by solving structures of rat TRPV2, both with and without an intact turret at resolutions of 4.0 angstrom and 3.6 angstrom, respectively. These structures resolve the full-length pore turret and reveal fully open and partially open states of TRPV2, both with unoccupied vanilloid pockets. Our results suggest a mechanism by which physiological signals, such as lipid binding, can regulate the lower gate and couple to the upper gate through a pore-turret-facilitated mechanism.