The molecular structure of the Toll-like receptor 3 ligand-binding domain
The molecular structure of the Toll-like receptor 3 ligand-binding domain
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DOI：
10.1073/pnas.0505077102
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发表时间：
2005-08-02
影响因子：
11.1
通讯作者：
Davies, DR
中科院分区：
文献类型：
--
作者：
Bell, JK;Botos, I;Davies, DR
先天免疫是抵抗病原体入侵的第一道防线。Toll样受体（TLR）作为先天免疫系统的哨兵，通过其由富含亮氨酸的重复序列（LRR）组成的配体结合结构域感测从脂多糖到鞭毛蛋白到dsRNA的多种配体。配体结合启动导致炎症介质上调的信号级联。在这项研究中，我们表达并结晶了人TLR 3的胞外域（ECD），它识别dsRNA，病毒的分子特征，并确定了分子结构到2.4埃分辨率。TLR 3-ECD的整体马蹄形结构由23个重复的LRR形成，其在每个末端被专门的非LRR结构域封端。分子凹面上广泛的β折叠形成了几种修饰的平台，包括插入LRR和11个Winked聚糖。TLR 3-ECD结构表明LRR环如何建立不同的病原体识别受体。
Innate immunity is the first line of defense against invading pathogens. Toll-like receptors (TLRs) act as sentinels of the innate immune system, sensing a variety of ligands from lipopolysaccharide to flagellin to dsRNA through their ligand-binding domain that is composed of leucine-rich repeats (LRRs). Ligand binding initiates a signaling cascade that leads to the up-regulation of inflammation mediators. In this study, we have expressed and crystallized the ectodomain (ECD) of human TLR3, which recognizes dsRNA, a molecular signature of viruses, and have determined the molecular structure to 2.4-angstrom resolution. The overall horseshoe-shaped structure of the TLR3-ECD is formed by 23 repeating LRRs that are capped at each end by specialized non-LRR domains. The extensive beta-sheet on the molecule's concave surface forms a platform for several modifications, including insertions in the LRRs and 11 Winked glycans. The TLR3-ECD structure indicates how LRR loops can establish distinct pathogen recognition receptors.