Beijing Key Laboratory of Animal Genetic Improvement, China Agricultural University, No.2 Yuanmingyuan West Rd, Haidian, Beijing, 100194, China.
College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, No.120 Dongling Rd, Shenhe, Shenyang, 110866, China.
J Mol Recognit. 2018 Jun;31(6):e2696. doi: 10.1002/jmr.2696. Epub 2017 Dec 27.
Toll-like receptors (TLRs) are an important part of the innate immune system, acting as a first line of defense against many invading pathogens. The ligand known to bind Gallus toll-like receptor 21 (gTLR21) is the unmethylated cytosine phosphate guanine dideoxy nucleotide motif; however, the evolutionary characteristics and structural biology of gTLR21 are poorly elaborated. Our results suggest that gTLR21 is phylogenetically and evolutionarily related to the TLR11 family and is perhaps a close ortholog of the Mus TLR13. Structural biology of homology modeling of the gTLR21 ectodomain structure suggests that it has no Z-loop like that seen in Mus TLR9. The cytosolic toll-IL-1 receptor region of gTLR21 contains a central 4-stranded parallel β-sheet (βA-βD) surrounded by 5 α-helices (αA-αE) on both sides, a highly conserved structure also seen in other TLRs. Molecular docking analysis reveals that the gTLR21 ectodomain has the potential to distinguish between different ligands. Homodimer analysis results also suggest that Phe842 and Pro844 of the BB loop and Cys876 of the αC helix in gTLR21 are conserved in other cytosolic toll-IL-1 receptor domains of other TLRs and may contribute to the docking of homodimers. Our study on the evolutionary characteristics and structural biology of gTLR21 reveals that the molecule may have a broader role to play in innate immune system; however, further experimental validation is required to confirm our findings.
Toll-like 受体 (TLRs) 是先天免疫系统的重要组成部分，作为抵御许多入侵病原体的第一道防线。已知与 Gallus toll-like receptor 21 (gTLR21) 结合的配体是未甲基化的胞嘧啶磷酸鸟嘌呤二脱氧核苷酸基序；然而，gTLR21 的进化特征和结构生物学尚未得到充分阐述。我们的研究结果表明，gTLR21 在系统发育和进化上与 TLR11 家族有关，可能是 Mus TLR13 的密切同源物。gTLR21 外域结构的同源建模结构生物学表明，它没有像 Mus TLR9 中那样的 Z 环。gTLR21 的胞质 toll-IL-1 受体区域包含一个中央 4 股平行 β-片层 (βA-βD)，两侧由 5 个 α-螺旋 (αA-αE) 环绕，这是其他 TLR 中也看到的高度保守结构。分子对接分析表明，gTLR21 的外域结构具有区分不同配体的潜力。同源二聚体分析结果还表明，gTLR21 的 BB 环中的 Phe842 和 Pro844 以及 αC 螺旋中的 Cys876 在其他 TLR 的胞质 toll-IL-1 受体结构域中是保守的，可能有助于同源二聚体的对接。我们对 gTLR21 的进化特征和结构生物学的研究表明，该分子可能在先天免疫系统中发挥更广泛的作用；然而，需要进一步的实验验证来证实我们的发现。
