Structural basis of toll-like receptor 3 signaling with double-stranded RNA
Structural basis of toll-like receptor 3 signaling with double-stranded RNA
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DOI：
10.1126/science.1155406
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发表时间：
2008-04-18
期刊：
影响因子：
56.9
通讯作者：
Davies, David R.
中科院分区：
文献类型：
--
作者：
Liu, Lin;Botos, Istvan;Davies, David R.
Toll样受体3（TLR 3）识别双链RNA（dsRNA），这是大多数病毒的分子特征，并引发阻止病毒传播的炎症反应。TLR 3胞外域（ECD）在长度为至少40至50个碱基对（信号转导所需的最小长度）的寡核苷酸上二聚化。为了建立配体结合和信号传导的分子基础，我们在3.4埃分辨率下确定了两个小鼠TLR 3-ECD和dsRNA之间的复合物的晶体结构。每个TLR 3- ECD在位于TLR 3马蹄铁相对末端的两个位点结合dsRNA，并且两个TLR 3- ECD C-末端结构域之间的分子间接触协调并稳定二聚体。这种并置可以通过使细胞质Toll白细胞介素-1受体（TIR）结构域二聚化来介导下游信号传导。TLR 3- ECD的整体形状在与dsRNA结合后不改变。
Toll- like receptor 3 ( TLR3) recognizes double- stranded RNA ( dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains ( ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3- ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3- ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3- ECD C- terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin- 1 receptor ( TIR) domains. The overall shape of the TLR3- ECD does not change upon binding to dsRNA.