Comparative structural analysis of haemagglutinin proteins from type A influenza viruses: conserved and variable features
| Autor: | Irene Righetto, Giovanni Cattoli, Francesco Filippini, Adelaide Milani |
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| Rok vydání: | 2014 |
| Předmět: |
Virus genetics
Antigenic drift Protein Conformation viruses Static Electricity Neuraminidase Hemagglutinin Glycoproteins Influenza Virus Avian influenza virus medicine.disease_cause Biochemistry Protein structure Structural Biology Molecular evolution Hydropathy analysis Influenza Human Influenza A virus medicine Humans Serologic Tests Homology modeling Viral evolution Molecular Biology Phylogeny Haemagglutinin biology Influenza A Virus H5N1 Subtype Applied Mathematics bioinformatics influenza aviaria H5N1 Virology Biological Evolution Isopotential contour Computer Science Applications Protein Structure Tertiary Evolutionary biology biology.protein Receptors Virus Research Article Receptor binding domain |
| Zdroj: | BMC Bioinformatics |
| ISSN: | 1471-2105 |
| Popis: | Background Genome variation is very high in influenza A viruses. However, viral evolution and spreading is strongly influenced by immunogenic features and capacity to bind host cells, depending in turn on the two major capsidic proteins. Therefore, such viruses are classified based on haemagglutinin and neuraminidase types, e.g. H5N1. Current analyses of viral evolution are based on serological and primary sequence comparison; however, comparative structural analysis of capsidic proteins can provide functional insights on surface regions possibly crucial to antigenicity and cell binding. Results We performed extensive structural comparison of influenza virus haemagglutinins and of their domains and subregions to investigate type- and/or domain-specific variation. We found that structural closeness and primary sequence similarity are not always tightly related; moreover, type-specific features could be inferred when comparing surface properties of haemagglutinin subregions, monomers and trimers, in terms of electrostatics and hydropathy. Focusing on H5N1, we found that variation at the receptor binding domain surface intriguingly relates to branching of still circulating clades from those ones that are no longer circulating. Conclusions Evidence from this work suggests that integrating phylogenetic and serological analyses by extensive structural comparison can help in understanding the ‘functional evolution’ of viral surface determinants. In particular, variation in electrostatic and hydropathy patches can provide molecular evolution markers: intriguing surface charge redistribution characterizing the haemagglutinin receptor binding domains from circulating H5N1 clades 2 and 7 might have contributed to antigenic escape hence to their evolutionary success and spreading. Electronic supplementary material The online version of this article (doi:10.1186/s12859-014-0363-5) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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