TRPV1 structures in distinct conformations reveal activation mechanisms.
TRPV1 structures in distinct conformations reveal activation mechanisms.
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作者：
TRP通道是多模态信号探测器，对广泛的物理和化学刺激作出反应。阐明这些通道如何整合并将生理信号转化为通道打开，对于理解它们如何在正常和病理生理条件下调节细胞兴奋性至关重要。在这里，我们利用药理学探针（肽毒素和小香草受体激动剂）来确定辣椒素受体TRPV1的两种激活状态的结构。在TRPV1中，电压门控通道激活过程中移动的域（S1-S4）保持静止，突出了这些结构相关通道超家族的门控机制差异。TRPV1的打开与外孔的主要结构重排有关，包括孔螺旋和选择性过滤器，以及下部闸门疏水收缩的明显扩张，表明双重闸门机制。上下门之间的变构耦合可能解释了TRPV1和其他TRP通道所表现出的丰富的生理调节。
TRP channels are polymodal signal detectors that respond to a wide range of physical and chemical stimuli. Elucidating how these channels integrate and convert physiological signals into channel opening is essential to understanding how they regulate cell excitability under normal and pathophysiological conditions. Here we exploit pharmacological probes (a peptide toxin and small vanilloid agonists) to determine structures of two activated states of the capsaicin receptor, TRPV1. A domain (S1-S4) that moves during activation of voltage-gated channels remains stationary in TRPV1, highlighting differences in gating mechanisms for these structurally related channel superfamilies. TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism. Allosteric coupling between upper and lower gates may account for rich physiologic modulation exhibited by TRPV1 and other TRP channels.
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影响因子：
16.2
作者：
Cao E;Cordero-Morales JF;Liu B;Qin F;Julius D
通讯作者：
Julius D
影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Brauchi, S;Orta, G;Latorre, R
通讯作者：
Latorre, R