Leucine-rich repeats and pathogen recognition in Toll-like receptors
Leucine-rich repeats and pathogen recognition in Toll-like receptors
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DOI：
10.1016/s1471-4906(03)00242-4
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发表时间：
2003-10-01
影响因子：
16.8
通讯作者：
Segal, DM
中科院分区：
文献类型：
--
作者：
Bell, JK;Mullen, GED;Segal, DM
Toll样受体（TLR）是对病原体炎症反应的主要细胞表面引发剂。它们通过其胞外结构域（ECD）结合多种致病物质。在这里，我们要问：这种相互作用的结构基础是什么？Toll样受体ECD包含19-25个串联拷贝的被称为富含亮氨酸重复序列（LRR）的基序。目前还没有TLR-ECD的X射线结构，但有几种高分辨率的含LRR的蛋白质可用于模拟TLR。我们认为TLRs的基本结构是一个马蹄形的螺线管，在其凹面上含有广泛的P-片层，以及许多配体结合插入物。总之，这些插入和P-折叠可以提供比抗体和T细胞受体中的结合表面大10倍的结合表面。
Toll-like receptors (TLRs) are the major cell-surface initiators of inflammatory responses to pathogens. They bind a wide variety of pathogenic substances through their ectodomains (ECDs). Here, we ask: what is the structural basis for this interaction? Toll-like receptor ECDs comprise 19-25 tandem copies of a motif known as the leucine-rich repeat (LRR). No X-ray structure of a TLR-ECD is currently available but there are several high-resolution LRR-containing proteins that can be used to model TLRs. We suggest that the basic framework of TLRs is a horseshoe-shaped solenoid that contains an extensive P-sheet on its concave surface, and numerous ligand-binding insertions. Together, these insertions and the P-sheet could provide a binding surface that is 10-fold greater in area than binding surfaces in antibodies and T-cell receptors.