风疹病毒E1蛋白与受体结合特定结合域的预测  

Prediction of specific binding domain of rubella virus E1 protein and its receptor

作　　者：邢家强[1] 刘晓凡[1] 窦强[1] 林杰[1] 魏至栋[1] 

机构地区：[1]兰州生物制品研究所有限责任公司,甘肃兰州730046

出　　处：《中国生物制品学杂志》2014年第6期756-760,共5页Chinese Journal of Biologicals

摘　　要：目的 同源模建E1蛋白及其受体髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein,MOG）的三维结构,应用分子对接的方法预测E1蛋白与其受体MOG的候选结合氨基酸残基。方法 采用MODELLER程序预测E1蛋白及其受体MOG的三维结构,并应用CASTp server进行活性口袋的预测;采用ProtScale进行疏水性分析,应用基于隐马尔可夫模型（HMM）算法的SMART程序搜索蛋白序列的motif;采用PyMOL-APBS软件设计E1蛋白及其受体MOG分子的腔介质结构,分析其表观静电势,应用PLATINUM程序进行分子对接,寻找其结合位点。结果E1蛋白由3个结构Ⅱ组成,其中D1、D3处于结构的底部,形成一个大的口袋,C-末端与D2的一侧形成另一个大的口袋,其余口袋主要集中在D2上半部的融合面中;MOG的结构模型为8个反平行的β折叠组成的一个β折叠桶,预测结构的主链构象的所有氨基酸均处于允许区。在MOG N-末端1～17位的氨基酸残基形成一个moti（flow complexityregion）,46～127位的氨基酸残基形成了一个motif V型免疫球蛋白样结构Ⅱ（Immunoglobulin V-Type,IGv）;lowcomplexity region段氨基酸残基表现为强疏水性。MOG N-末端的5个残基基序及ARG101～GLU107构成的β转角共同形成一个突起的结构,插入到E1蛋白的活性口袋中,与口袋中的ALA86、TYR90、TYR101、PHE102、ASN103、GLY105、SER107、TYR109、ALA122、PHE123、HIS125、SER126相互结合。结论 应用计算机模拟技术预测了E1蛋白与其受体MOG结合的特定结合Ⅱ,为今后进一步研究其相互作用奠定了基础。Objective To build the three-dimensional structure of rubella protein E1 and its receptor myelin oligodendrocyte glyeoprotein （MOG） by homologous modeling, and predict the candidate residues of E1 binding to MOG by molecular docking technique. Methods The three-dimensional structure of rubella protein E1 and its receptor MOG were predicted by MODELLER program, while the active packet by CASTp server. The hydrophobicity of MOG was analyzed by ProtScale method. The motif of protein was searched by Hidden Markov Model HMM-based SMART program. The cavity medium structures of E1 and MOG were designed by PyMOL-APBS software, while the electrostatic potentials were analyzed. The binding sites of were searched by molecular docking program PLATINUM. Results E1 protein consisted of three domains, of which D1 and D3 were at the bottom of structure and formed a big packet, while the C-terminus and one side of D2 formed another big packet. However, other packets were mainly centralized on the fusion surface of upper half part of D2. The structural model of MOG was a β-sheet barrel consisting of eight antiparallel sheets, while all the amino acid residues in main chain conformation of predicted structure were located in the permissible domains. The amino acids at sites 1 - 17 of N-terminus formed a motif （low complexity region）, while those at sites 46 - 127 formed an immunoglobulin V-type （IGv）. The amino acid residues in low complexity region showed strong hydrophobicity. The five amino acid residues at N-terminus of MOG and a β-turn consisting of ARG101 - GLU107 formed a spike-like structure which projected towards an active pocket located in a fusion surface framed by FL1 and FL2, and bound to ALAS6, TYR90, TYRI01, PHE102, ASN103, GLY105, SER107, TYR109, ALA122, PHE123, HIS125 and SER126 through hydrophobic interaction, hydrogen bond and aromatic stack. Conclusion The specific binding domain of E1 and MOG was predicted by computer modeling technique, which laid a foundation of further study on the interaction

关 键 词：风疹病毒 E1蛋白 三维结构 同源模建 分子对接 

分 类 号：R373.11[医药卫生—病原生物学]