人源TNF-α蛋白生物信息学分析及相关治疗思路研究  

Bioinformatics analysis of human TNF-α protein and related therapeutic ideas

作　　者：蹇艾利 申元英 姜石松 JIAN Aili;SHEN Yuanying;JIANG Shisong(Department of Microbiology and Immunology,School of Basic Medicine,Dali University,Dali,Yunnan 671000,China;Department of Oncology,University of Oxford,Oxford,the United Kingdom,Oxford OX37DQ,UK)

机构地区：[1]云南大理大学基础医学院微生物学及免疫学教研室,云南大理671000 [2]英国牛津大学肿瘤系,英国牛津OX37DQ

出　　处：《现代医药卫生》2022年第12期1981-1985,共5页Journal of Modern Medicine & Health

基　　金：国家自然科学基金项目(81641095)。

摘　　要：目的应用生物信息学分析软件预测并分析人源肿瘤坏死因子-α(TNF-α)蛋白结构和功能,并结合该课题组前期实验结果提出一些新的治疗思路。方法利用在线Uniprot蛋白数据库、Expasy在线预测网站、SignalP-5.0、TMHMM Server V2.0、Cell-Ploc、SOPMA、SWISS-MODEL、在线数据库Protscale等生物信息学预测软件对人源TNF-α蛋白理化性质、信号肽、跨膜区、亚细胞定位、空间结构及疏水性分析;登录“http://www.cbs.dtu.dk/services/netrhos/”网站对该蛋白磷酸化位点进行预测;选取String及IEDB等在线网站分析人源TNF-α的相互作用蛋白及该蛋白优势表位预测。结果人源TNF-α蛋白为编码233个氨基酸的蛋白质,相对分子质量为26×10^(3),为不太稳定的亲水性蛋白,有跨膜区,无信号肽;预测该蛋白亚细胞定位在细胞膜中,蛋白序列中存在15个丝氨酸磷酸化位点,二级结构以α-螺旋和无规则卷曲为主;三级结构模型显示该蛋白可形成同源三聚体,有多种蛋白与之相互作用。结论生物信息学预测分析人源TNF-α含有多个磷酸化位点和B细胞优势表位,并且该表位与前期实验找到的功能性肽段序列相符,可为临床针对人源TNF-α设计多肽或药物提供新靶点。Objective To predict and analyze the structure and function of human TNF-α protein by using bioinformatics analysis software,and to propose some new therapeutic ideas combined with the previous experiments results of the research group.Methods The physicochemical properties,signal peptide,transmembrane region,subcellular localization,spatial structure and hydrophobicity of human TNF-α protein were analyzed by bioinformatics prediction software including the online Uniprot protein database,Expasy online prediction website,SignalP-5.0,TMHMM Server V2.0,Cell-Ploc,SOPMA,SWISS-MODEL and Protscale.At“http://www.cbs.dtu.dk/services/netrhos/”to estimate the protein phosphorylation sites;Online sites such as String and IEDB were selected to analyze the interaction protein of human TNF-αand predict the dominant epitope of the protein.Results Human TNF-α protein was an unstable hydrophilic protein with a molecular weight of 26×10^(3),encoding 233 amino acids.It had the transmembrane region and no signal peptide.It was predicted that the subcellular localization of the protein was in the cell membrane,there were 15 serine phosphorylation sites in the protein sequence,and the secondary structure of the protein was mainly α-helix and random coil.The tertiary structure model showed that the protein could form homologous trimer and multiple proteins interacted with it.Conclusion Bioinformatics predict that the human TNF-α contains multiple phosphorylation sites and dominant B cell epitopes,and the epitopes are consistent with the functional peptide sequences found by the previous research group,which can provide a new target for clinical design of peptides or drugs targeting human TNF-α.

关 键 词：肿瘤坏死因子-Α 生物信息学分析 治疗 预测 

分 类 号：R318.04[医药卫生—生物医学工程]