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首页> 外文会议>International conference of molecular simulations and applied informatics technologies >Homology model and potential virus-capsid binding site of a putative HEV receptor Grp78
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Homology model and potential virus-capsid binding site of a putative HEV receptor Grp78

机译：推定HEV受体GRP78推定HEV受体的同源模型及潜在病毒衣壳粘结位点

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P239, a truncated construct of the hepatitis E virus (HEV) ORF2 protein, has been proven able to bind with a chaperone, Grp78, in both an in vitro co-immune precipitation test and an in vivo cell model. We previously solved the crystal structure of E2s-the Cterminal domain of p239 involved in host interactions. In the present study, we built a 3D structure of Grp78 using homology modeling methods, and docked this molecule with E2s using the Zdockpro module of the Insightll software package. The modeled Grp78 structure was deemed feasible by profile 3D evaluation and molecular dynamic simulations. The docking result consists of six clusters of distinct complexes and C035 was selected as the most reasonable. The interacting interface of the predicted complex is comprised of the Grp78 linker region and nucleotide binding domain along with the E2s groove region and surrounding loops. Using energy, hydrogen bond and solvent accessible surface analyses, we identified a series of key residues that may be involved in the Grp78:E2s interaction. By comparing with the known structure of the Hsp70:J complex, we further concluded that the interaction of Grp78 and E2s could interrupt binding of Grp78 with the J domain, and in turn diminish or even eliminate the binding ability of the Grp78 substrate binding domain. The predicted series of key residues also provides clues for further research that should improve our understanding of the fundamental molecular mechanisms of HEV infection.
机译：P239是一种截断的丙型肝炎病毒（HEV）ORF2蛋白的构建体，已被证明能够与体外共免疫沉淀试验和体内细胞模型中的伴侣酮GRP78结合。我们以前解决了E2S的晶体结构 - 宿主相互作用的P239的触髓域。在本研究中，我们使用同源性建模方法建立了GRP78的3D结构，并使用Insightwl软件包的ZdockPro模块将此分子与E2S一起停靠。通过简档3D评估和分子动态模拟认为，建模的GRP78结构被视为可行。对接结果由六个不同的复合物组成，选择C035作为最合理的。预测复合物的相互作用界面由GRP78接头区域和核苷酸结合结构域组成，以及E2S槽区域和周围环绕环。使用能量，氢键和溶剂可接近的表面分析，我们确定了一系列可能参与GRP78：E2S相互作用的关键残留物。通过与Hsp70的已知结构比较：J-复杂，我们进一步认为，Grp78的和E2同样的相互作用可能会中断与J域Grp78的结合，进而减退或甚至消除Grp78的底物结合结构域的结合能力。预测系列的关键残留还提供了进一步研究的线索，这应该改善我们对HEV感染的基本分子机制的理解。

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