Structural insight into TRPV5 channel function and modulation
Structural insight into TRPV5 channel function and modulation
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DOI：
10.1073/pnas.1820323116
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发表时间：
2019-04-30
影响因子：
11.1
通讯作者：
van der Wijst, Jenny
中科院分区：
文献类型：
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作者：
Dang, Shangyu;van Goor, Mark K.;van der Wijst, Jenny
瞬时受体电位香草酸5（TRPV5）是一种独特的钙选择性TRP通道，对钙稳态至关重要。与其他TRPV通道不同，TRPV5及其同源物TRPV6不表现出热敏性或配体依赖性激活，但在生理膜电位下组成性开放，并以钙依赖性方式受钙调蛋白（CaM）调节。在这里，我们报告高分辨率的电子冷冻显微镜结构的截断和全长TRPV5的脂质纳米盘，以及TRPV5 W583A突变体和TRPV5与钙调素复合物。这些结构突出了钙调节的机制，并揭示了一个灵活的化学计量的钙调素结合TRPV5。
TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.