Protein intrinsic disorder toolbox for comparative analysis of viral proteins

Abstract

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.

Figure 1

Model structures of the influenza A (A) and HIV-1 (B) virions.

Figure 2

Chart summarizing the percentages of residues predicted to be disordered in HIV-1 (A) and the influenza A virus proteins (B). Top of each panel represents chart of proteins with percentages of residues that are predicted to be disordered by PONDR^® VLXT. The types of proteins are also summarized. It should be noted that the percentages of predicted to be disordered residues of HA vary with subtypes, but HA is essentially predicted to be quite ordered. More information is available in Table 5.

Figure 3

An entity-relationship (ER) diagram of the viral protein database. Each entity contains attributes. The type of relationships is shown by the connector and/or the black circle. For example, a black circle followed by dotted line indicates a many to zero or one relationship. Whereas, the black circle followed by a solid line indicates a many to one relationship [76].