Analysis of the three-dimensional structure of the African horse sickness virus VP7 trimer by homology modelling
Analysis of the three-dimensional structure of the African horse sickness virus VP7 trimer by homology modelling
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DOI：
10.1016/j.virusres.2017.02.001
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发表时间：
2017-03-15
期刊：
影响因子：
5
通讯作者：
van Staden, Vida
中科院分区：
文献类型：
--
作者：
Bekker, Shani;Burger, Pieter;van Staden, Vida
VP 7是环状病毒的主要核心蛋白，并且对于病毒体装配是必需的。非洲马瘟病毒（AHSV）VP 7自组装成高度不溶性的结晶颗粒-这一属性可能与AHSV VP 7在病毒组装中的作用有关，但也会阻止结晶。鉴于这种固有的不溶性是AHSV VP 7所独有的，我们使用AHSV VP 7和其他环状病毒之间的氨基酸序列保守性分析来鉴定驱动AHSV VP 7自组装的推定关键残基。生成AHSV VP 7三聚体的同源性模型以分析三聚体的表面性质并鉴定作为驱动AHSV VP 7自组装的AHSV VP 7三聚体-三聚体相互作用的候选物的表面残基。鉴定了9个区域作为未来定点诱变实验的候选残基，这些实验可能产生可溶性AHSV VP 7蛋白。此外，我们鉴定了在AHSV VP 7三聚体内的分子间相互作用中起作用的推定残基以及几个表位。鉴于之前溶解AHSV VP 7的许多努力，我们提出了一种有用的策略，该策略将产生可溶性AHSV VP 7，可用于研究AHSV组装并提高重组疫苗制剂的产量。(C)2017爱思唯尔B. V.保留所有权利。
VP7 is the major core protein of orbiviruses and is essential for virion assembly. African horse sickness virus (AHSV) VP7 self-assembles into highly insoluble crystalline particles - an attribute that may be related to the role of AHSV VP7 in virus assembly but also prevents crystallization. Given that this inherent insolubility is unique to AHSV VP7, we use amino acid sequence conservation analysis between AHSV VP7 and other orbiviruses to identify putative key residues that drive AHSV VP7 self-assembly. A homology model of the AHSV VP7 trimer was generated to analyze surface properties of the trimer and to identify surface residues as candidates for the AHSV VP7 trimer-trimer interactions that drive AHSV VP7 self-assembly. Nine regions were identified as candidate residues for future site-directed mutagenesis experiments that will likely result in a soluble AHSV VP7 protein. Additionally, we identified putative residues that function in the intermolecular interactions within the AHSV VP7 trimer as well as several epitopes. Given the many previous efforts of solubilizing AHSV VP7, we propose a useful strategy that will yield a soluble AHSV VP7 that can be used to study AHSV assembly and increase yield of recombinant vaccine preparations. (C) 2017 Elsevier B.V. All rights reserved.