Structure of the full-length TRPV2 channel by cryo-EM.
Structure of the full-length TRPV2 channel by cryo-EM.
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DOI：
10.1038/ncomms11130
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发表时间：
2016-03-29
影响因子：
16.6
通讯作者：
Moiseenkova-Bell VY
中科院分区：
文献类型：
--
作者：
Huynh KW;Cohen MR;Jiang J;Samanta A;Lodowski DT;Zhou ZH;Moiseenkova-Bell VY
瞬时受体电位(Trp)蛋白形成一个超家族钙离子渗透性阳离子通道，受一系列化学和物理刺激的调节。对一个‘最小’色氨酸香草酸亚型1(TRPV1)的结构分析阐明了激动剂通过改变其外孔区激活通道的机制。虽然与TRPV1同源，但其他TRPV通道(TRPV2-6)对包括热和香草素在内的TRPV1激动剂不敏感。为了进一步了解TRPV通道功能的结构基础，我们用冷冻电子显微镜在∼5 ä分辨率下确定了全长TRPV2的结构。与TRPV1一样，TRPV2含有两个狭窄，在成孔的上下门各有一个。与封闭和激动剂激活的TRPV1相比，不含激动剂的全长TRPV2具有更宽的上下闸门。我们认为这些新发现的TRPV2结构特征有助于TRPV通道的多样性。瞬时受体电位(Trp)蛋白是一种可被一系列化学和物理刺激激活的钙离子通透性阳离子通道。在这里，作者描述了全长TRPV2通道的低温EM结构，它提供了对TRPV亚家族通道调控的洞察。
Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a ‘minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2–6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels. Transient receptor potential (TRP) proteins are Ca2+-permeable cation channels activated by a range of chemical and physical stimuli. Here the authors describe a cryo-EM structure of the full-length TRPV2 channel that provides insight into the regulation of the TRPV subfamily of channels.