Analysis of the three-dimensional structure of the African horse sickness virus VP7 trimer by homology modelling.
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.
Department of Genetics, University of Pretoria, Pretoria 0002, South Africa.
Shani
S
Bekker
Bioinformatics and Computational Biology Unit, University of Pretoria, Pretoria 0002, South Africa.
Pieter
P
Burger
Department of Genetics, University of Pretoria, Pretoria 0002, South Africa. Electronic address: vida.vanstaden@up.ac.za.
Vida
V
van Staden
D000356:African Horse Sickness Virus / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D001820:Bluetongue virus / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018604:Epitope Mapping; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D014758:Viral Core Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D019065:Virus Assembly
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D014758:Viral Core Proteins; C066862:VP7 protein, orbivirus; C069264:VP7 major core antigen, African horsesickness virus
AHSV; Epitopes; Homology modelling; Self-assembly; Trimer; VP7