摘要
目的利用生物信息学分析抑制抗原加工相关转运体(TAP)肽转运的伪狂犬病病毒(PRV)蛋白。方法和用在线分析软件分析HSV-1 ICP47,BoHV-1 UL49.5.HCMV US6.EBV BNLF2a.CPXV CPXV012等5种已知TAP抑制剂的理化性质、疏水性跨膜域、磷酸化修饰、亚细胞定位、信号肽、二级结构等,筛选出与几种TAP抑制剂相似的PRV蛋白,并对TAP抑制剂和筛选出的PRV蛋白进行同源比对及三级结构预测和分析比较。结果筛选出与TAP抑制剂BoHV-1 UL49.5同样存在--个信号肽、两个跨膜域、主要定位于内质网且核背酸同源性为52.0%的疏水性蛋白PRV gN(UL49.5),以及与HCMV US6同样存在一个信号肽、一个跨膜域、主要定位于质膜和内质网且核昔酸同源性分别为44.9%和47.1%的亲水性蛋白PRV gD(US6)和PRV gC(UL44)。筛选蛋白与同源性较高的TAP抑制剂理化性质、亚细胞定位,跨膜域、二级结构等基本类似。结论PRV蛋白的gN(UIL49.5)、gD(US6)和gC(UL44)可能影响TAP的肽转运功能,本研究为揭示TAP介导的PRV蛋白免疫逃逸机制和为与TAP相关的靶向治疗研究提供了理论基础。
Objective To use bioinformatics 10 predict pseudorabies virus(PRV)proteins that inhibit transporter as-sociated with antigen processing(TAP)peptide transport.Methods First.the physicochemical properties of 5 known TAP inhibitors and PRV proteins were analyzed using the program Protparam in Expasy.Next,signal peptides of TAP inhibitors and PRV proteins with similar physicochemical properties were analyzed using the software SignalIP.The sub-cellular localization of similar protein groups was determined by analyzing signal peptides with the software PSORT,The phos phorylation sites of TAP inhibitors and PRV proteins with similar structures across the membrane were subsequently determined with the program NetPhos 2.0.and the homology of TAP inhibitors and PRV proteins with similar structures were compared using the comparison tool Megaline in the software DNAStar.The secondary structures of relatively simi-lar proteins were analyzed using the online software SOPMA,and homology modeling was performed using SWIss MOD-EL.last.the three dimensional structures of the proteins were compared using RSCBPDB.Results Three PRV pro-teins with structures similar to known T AP inhibitors were identified.These proteins are the hydrophobie protein PRV gN(UL49.5),which has a nucleotide similarity of 52.0%to the TAP inhibitor BoHV-1 UL49.5,and the hydrophilie proteins PRV gD(US6)and PRV gC(UL44),which have日respective nucleotide similarity of 44.9%and 47.1%to HCMV US6.PRV gN(UL49,5)has one signal peptide and two transmermbrane dormains and is located in the endoplas-mic reticulum like BoHV-1 UL49.5,and PRV gD(US6)and PRV gC(UL44)have one signal peptide and one trans-membrane domain and are located in the plasma membrane and endoplasmic reticulum like HCMV US6.The screened proteins are basically similar to TAP inhibitors with greater similarity in terms of physicochernical properties,subcellular localization.transmembrane domains.and secondary structure.Conclusion In addition to the reported gN(UL49,5)of PRV protein,gD(US6)and gC(UL44)may also afct the peptide Iransport function of TAP.This study provides a theoretical foundation to elucidate the mechanism of immune escape of the PRV protein mediated by TAP and the future study of targeted therapy related to TAP.
作者
马宁宁
刘占
史志斌
赵小月
邓梦梦
郭子仪
陈陆
MA Ning-ning;LIU Zhan;SHI Zhi-bin;ZHAO Xiao-yue;DENG Meng-meng;GUO Zi-yi;CHEN Lu(Institute for the Prevenion of Arimal Infectious Diseases,De partment of Veterinary Medicine,Henan Agri-culsural University,Zhengzhou,China 450000)
出处
《中国病原生物学杂志》
CSCD
北大核心
2019年第12期1386-1393,共8页
Journal of Pathogen Biology
基金
国家自然科学基金项目(No.31772781).
