【摘 要】
：
Background: Toll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via
【机 构】
：
Beijing Institute of Biotechnology,Beijing 100071, China
【出 处】
：
第七届国际分子模拟与信息技术应用学术会议
论文部分内容阅读
Background: Toll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via the adaptor protein MyD88.However, the specific sequence and structural requirements of the CpG DNA for the recognition of and binding to TLR9 are unknown.Moreover, the 3D structures of TLR9 and the TLR9-ODN complex have not been determined.In this study, we propose a reliable model of the interaction of the TLR9 ECD with CpG ODN using bioinformatics tools.Results: The three-dimensional structures of two TLR9 ECD-CpG ODN complexes were constructed using a homology modelling and docking strategy.Based on the models of these complexes, the TLR9 ECD-CpG ODN interaction patterns were calculated.The results showed that the interface between the human TLR9 and the CpG ODN molecule is geometrically complementary.The computed molecular interactions indicated that LRR11 is the main region of TLR9 that binds to CpG ODN and that five positively charged residues within LRR11 are involved in the binding of the TLR9 ECD to the CpG ODN.Observations in the close-up view of these interactions indicated that these five positively charged residues contribute differently to the binding region within the TLR9 ECD-CpG ODN complex.337Arg and 338Lys reside in the binding sites of ODN, forming hydrogen bonds and direct contacts with the CpG ODN, whereas 347Lys, 348Arg, and 353His do not directly contact the CpG ODN.These results are in agreement with previously reported experimental data.Conclusion: In this study, we present two structural models for the human and mouse TLR9 ECD in a complex with CpG ODN.Some features predicted by this model are consistent with previously reported experimental data.This complex model may lead to a better understanding of the function of TLR9 and its interaction with CpG ODN and will improve our understanding of TLR9-ligand interaction in general.
其他文献
Avian coccidiosis, caused by Eimeria spp., is one of the major parasitic diseases in birds.Cysteine protease is a major virulence factor in parasitic protozoa, and it may be a suitable chemotherapeuti
RNA-binding proteins play critical roles in various cellular processes.Computational approaches to identify RNA-binding proteins have an important guiding role in designing experiments in RBPome.In th
CMG2-Fc is a fusion protein composed of the extracellular domain of capillary morphogenesis protein 2 (CMG2) and the Fc region of human immunoglobulin G;CMG2-Fc neutralizes anthrax toxin and offers pr
A series of oxime ether acylhydrazone derivative (3a-3s) were synthesized and fully characterized by 1H NMR and 13C NMR.The crystal structure of compound 3b was further determined by single-crystal X-
The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity.Alt
Owing to its unique function to release the progeny virus particles from the surface of an infected cell, neuraminidase has drawn special attention for developing new drugs to treat influenza viruses.
The 3D chromatin structure modeling by chromatin interactions derived from Hi-C experiments is significantly challenged by the intrinsic sequencing biases in these experiments.Conventional modeling me
For biosynthesis of bacillamide C by Bacillus atrophaeus C89 associated with South China sea sponge Dysidea avara, it is hypothesized that decarboxylation from L-tryptophan to tryptamin e could be per
The interaction of copper compounds with DNA is significant in a variety of biological processes [1].A series of six molecular dynamics simulations were performed to investigate the interaction betwee
The thermophilic intracellular protease (PH1704) from Pyrococcus horikoshii that functions as an oligomer (hexamer or higher forms) has proteolytic activity and remarkable stability.PH1704 is classifi