The evolutionary characteristics and structural biology of Gallus toll-like receptor 21.

The evolutionary characteristics and structural biology of Gallus toll-like receptor 21.
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原鸡toll样受体21的进化特征和结构生物学

DOI:
10.1002/jmr.2696
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发表时间:
2018-06
期刊:
Journal of molecular recognition : JMR
影响因子:
--
通讯作者:
Lian Z
Lian Z
中科院分区:
其他
文献类型:
--
作者:
Wu H;Wang H;Jiang W;Lian Z

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Toll样受体(TLR)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。已知结合Gallus toll样受体21(gTLR 21)的配体是未甲基化的胞嘧啶磷酸鸟嘌呤双脱氧核苷酸基序;然而,gTLR 21的进化特征和结构生物学阐述不多。我们的研究结果表明,gTLR 21在遗传和进化上与TLR 11家族相关,并且可能是小鼠TLR 13的直系同源物。gTLR 21胞外域结构的同源性建模的结构生物学表明,它没有像小鼠TLR 9中所见的Z环。gTLR 21的胞质toll-IL-1受体区包含一个中心4链平行β折叠(βA-βD),两侧被5个α螺旋(αA-αE)包围,这是一种在其他TLR中也可见的高度保守结构。分子对接分析表明,gTLR 21胞外域具有区分不同配体的潜力。同源二聚体分析结果还表明,gTLR 21中BB环的Phe 842和Pro 844以及αC螺旋的Cys 876在其他TLR的其他胞质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gTLR 21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。
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.
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