Ditsinctive Recognition of Flagellin by Human and Mouse Toll-Like Receptor 5
Ditsinctive Recognition of Flagellin by Human and Mouse Toll-Like Receptor 5
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DOI：
10.1371/journal.pone.0158894
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发表时间：
2016-07-08
期刊：
影响因子：
3.7
通讯作者：
Bencina, Mojca
中科院分区：
文献类型：
--
作者：
Forstneric, Vida;Ivicak-Kocjan, Karolina;Bencina, Mojca
Toll 样受体 5 (TLR5) 是先天免疫系统的一种受体，可识别某些细菌物种的鞭毛蛋白并引发炎症反应。都柏林沙门氏菌鞭毛蛋白与斑马鱼 TLR5 的复合物先前已结晶。在本研究中，我们使用结构引导诱变推断该复合物的结构，以确定人和小鼠 TLR5 受体的识别模式，并证明鞭毛蛋白识别的物种特异性差异。总的来说，小鼠受体的识别模式可以说比人类受体的识别模式更加稳健。全原子分子动力学模拟显示了主要结合区域内两种受体之间的差异。使用功能运动测定，我们表明，尽管本研究中分析的鞭毛蛋白的高度保守区域包含鞭毛形成的关键结构要求，但没有观察到免疫识别和氨基酸残基水平上的结构之间的直接相关性。
Toll-like receptor 5 (TLR5) is a receptor of the innate immune system that recognizes flagellin from certain bacterial species and triggers an inflammatory response. The Salmonella dublin flagellin in complex with zebrafish TLR5 has been crystallized previously. In the present study, we extrapolate the structure of this complex using structure-guided mutagenesis to determine the recognition modes of human and mouse TLR5 receptors and demonstrate species-specific differences in flagellin recognition. In general, the recognition mode of the mouse receptor can be said to be more robust in comparison to that of the human receptor. All-atom molecular dynamics simulation showed differences between the two receptors within the primary binding region. Using a functional motility assay, we show that although the highly conserved area of the flagellin analyzed in this study encompasses key structural requirements for flagella formation, a direct correlation between immune recognition and structure on the level of amino acid residues is not observed.