Protein intrinsic disorder toolbox for comparative analysis of viral proteins.
To examine the usefulness of protein disorder predictions as a tool for the comparative analysis of viral proteins, a relational database has been constructed. The database includes proteins from influenza A and HIV-related viruses. Annotations include viral protein sequence, disorder prediction, structure, and function. Location of each protein within a virion, if known, is also denoted. Our analysis reveals a clear relationship between proximity to the RNA core and the percentage of predicted disordered residues for a set of influenza A virus proteins. Neuraminidases (NA) and hemagglutinin (HA) of major influenza A pandemics tend to pair in such a way that both proteins tend to be either ordered-ordered or disordered-disordered by prediction. This may be the result of these proteins evolving from being lipid-associated. High abundance of intrinsic disorder in envelope and matrix proteins from HIV-related viruses likely represents a mechanism where HIV virions can escape immune response despite the availability of antibodies for the HIV-related proteins. This exercise provides an example showing how the combined use of intrinsic disorder predictions and relational databases provides an improved understanding of the functional and structural behaviour of viral proteins.
Goh
Gerard Kian-Meng
GK
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. gerard@compbio.iupui.edu
Dunker
A Keith
AK
Uversky
Vladimir N
VN
D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology; D003628:Database Management Systems; D030562:Databases, Protein; D006678:HIV / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D054298:Human Immunodeficiency Virus Proteins