「瞬時受體電位」(TRP)通道是一系列物理和化學刺激的傳感器。
在兩篇相關聯論文的第一篇中,Maofu Liao 等人獲得了大鼠TRPV1(辣椒素受體——辣椒素是辣椒中的辛辣成分)在一個「封閉」狀態下的高解析度低溫電子顯微鏡結構。該結構總體上與電壓門控的離子通道的結構相當相似,但有TRP通道特有的幾個結構特點。
在第二篇論文中,Erhu Cao等人發表了大鼠TRPV1在一種肽神經毒素(Resiniferatoxin)存在時和在辣椒素存在時的結構,從而提供了該通道激活狀態的結構。對閉合和開啟狀態下的結構所做比較顯示,TRPV1有一個獨特的雙門通道激活機制。(生物谷Bioon.com)
生物谷推薦的英文摘要
Nature doi:10.1038/nature12822
Structure of the TRPV1 ion channel determined by electron cryo-microscopy
Maofu Liao,Erhu Cao,David Julius& Yifan Cheng
Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 (S5–S6) and the intervening pore loop, which is flanked by S1–S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 『mouth』 with a short selectivity filter. The conserved 『TRP domain』 interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.
doi:10.1038/nature12823
TRPV1 structures in distinct conformations reveal activation mechanisms
Erhu Cao,Maofu Liao,Yifan Cheng& David Julius
Transient receptor potential (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 (consisting of transmembrane segments 1–4) 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 physiological modulation exhibited by TRPV1 and other TRP channels.