Proceeding talk – Theme: Proteins.
Abstract
Due to their high genomic variability, RNA viruses, and Lentiviruses in particular, present a unique opportunity for detailed study of molecular evolution: thousands of sequences and three-dimensional structures are available. We use these data to study specific patterns of evolution of viral proteins, and their relationship to protein interactions and immunogenicity. We identify extremely conserved and extremely variable clusters of residues for animal immunodeficiency viruses. These clusters are located on the interaction interfaces with other proteins. In the immunodeficiency viruses, the interaction interfaces are not more conserved than protein surface on average, and we show that conserved clusters coincide with protein-protein interaction hotspots. Extremely variable clusters have been identified here for the first time. In the HIV-1 envelope protein they overlap with known antigenic sites. These antigenic sites also contain residues from extremely conserved clusters, hence representing unique interacting interfaces. This observation may have important implication for antiretroviral vaccine development.
Authors
Olga Voitenko, Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbruecken, Germany
Andi Dhroso, Department of Computer Science and Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, United States
Anna Feldmann, Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbruecken, Germany
Dmitry Korkin, Department of Computer Science and Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, United States
Olga Kalinina, Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbruecken, Germany