Structural Insight into the Assembly of TRPV Channels
Structural Insight into the Assembly of TRPV Channels
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DOI：
10.1016/j.str.2013.11.008
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发表时间：
2014-02-04
期刊：
影响因子：
5.7
通讯作者：
Moiseenkova-Bell, Vera Y.
中科院分区：
文献类型：
--
作者：
Huynh, Kevin W.;Cohen, Matthew R.;Moiseenkova-Bell, Vera Y.
瞬时受体电位（TRP）蛋白是一个大家族的多模态非选择性阳离子通道。TRP香草素（TRPV）亚家族由六个具有不同功能的同源成员组成。TRPV 1-TRPV 4是非选择性阳离子通道，被认为在伤害感受中起作用，而TRPV 5和TRPV 6参与上皮Ca 2+稳态。在这里，我们提出了冷冻电子显微镜（cryo-EM）结构的功能，全长TRPV 2在13.6埃的分辨率。图谱显示TRPV 2胞质结构域显示4倍花瓣状形状，其中高分辨率N-末端锚蛋白重复结构域（ARD）结构可以明确拟合。拟合其他TRPV亚科成员的ARD结构到TRPV 2 EM图表明，TRPV亚科成员具有高度同源的结构拓扑。这些结果使我们能够假设TRPV通道之间的功能多样性和蛋白质和配体的差异调节的结构解释。
Transient receptor potential (TRP) proteins are a large family of polymodal nonselective cation channels. The TRP vanilloid (TRPV) subfamily consists of six homologous members with diverse functions. TRPV1-TRPV4 are nonselective cation channels proposed to play a role in nociception, while TRPV5 and TRPV6 are involved in epithelial Ca2+ homeostasis. Here we present the cryo-electron microscopy (cryo-EM) structure of functional, full-length TRPV2 at 13.6 angstrom resolution. The map reveals that the TRPV2 cytoplasmic domain displays a 4-fold petal-like shape in which high-resolution N-terminal ankyrin repeat domain (ARD) structures can be unambiguously fitted. Fitting of the available ARD structures for other TRPV subfamily members into the TRPV2 EM map suggests that TRPV subfamily members have highly homologous structural topologies. These results allowed us to postulate a structural explanation for the functional diversity among TRPV channels and their differential regulation by proteins and ligands.