Zika virus envelope - heat shock protein A5 (GRP78) binding site prediction
Zika virus envelope - heat shock protein A5 (GRP78) binding site prediction
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DOI：
10.1080/07391102.2020.1784794
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发表时间：
2020-06-23
影响因子：
4.4
通讯作者：
Ibrahim, Ibrahim M.
中科院分区：
文献类型：
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作者：
Elfiky, Abdo A.;Ibrahim, Ibrahim M.
最近的研究报告称，寨卡病毒（ZIKV）与宿主细胞膜上的应激反应受体有关，该受体有助于病毒进入。这种宿主受体是热休克蛋白A5 (HSPA5)，也称为葡萄糖调节蛋白78 （GRP78）。本研究利用结构生物信息学和分子动力学模拟方法，确定了寨卡病毒包膜蛋白与细胞表面GRP78相互作用过程中的结合位点。正如之前报道的那样，Pep42环肽被用作筛选器，选择性地靶向癌细胞膜上的GRP78。序列和结构比对表明，部分寨卡病毒包膜蛋白（C308-C339区）除了具有环状结构外，在序列和结构上与环状Pep42相似。ZIKV包膜中的三个氨基酸与Pep42肽中的氨基酸相同。研究了环肽动力学，并预测了其与GRP78的结合。进一步进行蛋白-蛋白对接，探索寨卡病毒包膜与GRP78的结合特性。结果表明，寨卡病毒包膜蛋白与GRP78结合良好。对接姿态揭示了GRP78底物结合结构域ss和ZIKV包膜蛋白结构域III参与了病毒对宿主细胞的识别。
Recent studies reported the association of the Zika virus (ZIKV) with a stress response receptor on the host cell membrane that facilitates viral entry. This host receptor was the heat shock protein A5 (HSPA5), also termed glucose-regulating protein 78 (GRP78). In this study, structural bioinformatics and molecular dynamics simulations were utilized to suggest the binding site of ZIKV envelope protein during the interaction with cell-surface GRP78. The Pep42 cyclic peptide was used as a profiler, as it was reported earlier, to target GRP78 on the cancer cell membrane selectively. Sequence and structural alignments show that part of the ZIKV envelope protein (C308-C339 region), in addition to its cyclic nature, has somehow sequence and structural similarities to the cyclic Pep42. Three amino acids in the ZIKV envelope were identical to those in the Pep42 peptide. Cyclic peptides dynamics are studied, and its binding to GRP78 is predicted. Protein-protein docking is further performed to explore the binding characteristics of the ZIKV envelope to GRP78. Results revealed that the binding was favorable between ZIKV envelope protein and GRP78. The docking pose revealed the involvement of the substrate-binding domain ss of GRP78 and the domain III of the ZIKV envelope protein in viral recognition for the host-cell.