Wang Jinlan, Zhang Zheng, Chang Fen, Yin Deling
Institute of Developmental Biology, School of Life Science, Shandong University , Jinan , China.
State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan , China.
PeerJ. 2016 May 25;4:e2079. doi: 10.7717/peerj.2079. eCollection 2016.
Toll-like receptors (TLRs) play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein-protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops and αC-helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation.
Toll样受体（TLRs）在先天性免疫系统中发挥着重要作用。据报道，TLR15在抵御病原体方面具有独特作用，但其结构和进化特征仍知之甚少。在本研究中，我们从鸟类和爬行动物基因组中鉴定出57个完整的TLR15基因。TLR15聚集成一个单独的进化枝，在系统发育树上与第1家族密切相关。与第1家族中中间天冬酰胺梯子断裂的TLRs不同，TLR15胞外域有一个完整的天冬酰胺梯子，这对维持胞外域的整体形状至关重要。保守性分析发现，TLR15胞外域在LRR11模块的凸面上有一个高度进化保守区域，这可能参与TLR15的激活过程。此外，蛋白质-蛋白质对接分析表明，TLR15 TIR结构域有形成同源二聚体的潜力，TIR二聚体的预测相互作用界面主要由BB环和αC螺旋的残基形成。虽然TLR15主要经历纯化选择，但我们检测到TLR15有27个正选择位点，其中24个位于其胞外域。我们的观察结果表明了TLR15的结构特征可能与其功能相关，但这需要进一步的实验验证。
