A comparative analysis of viral matrix proteins using disorder predictors

Abstract

Background: A previous study (Goh G.K.-M., Dunker A.K., Uversky V.N. (2008) Protein intrinsic disorder toolbox for comparative analysis of viral proteins. BMC Genomics. 9 (Suppl. 2), S4) revealed that HIV matrix protein p17 possesses especially high levels of predicted intrinsic disorder (PID). In this study, we analyzed the PID patterns in matrix proteins of viruses related and unrelated to HIV-1.

Results: Both SIVmac and HIV-1 p17 proteins were predicted by PONDR VLXT to be highly disordered with subtle differences containing 50% and 60% disordered residues, respectively. SIVmac is very closely related to HIV-2. A specific region that is predicted to be disordered in HIV-1 is missing in SIVmac. The distributions of PID patterns seem to differ in SIVmac and HIV-1 p17 proteins. A high level of PID for the matrix does not seem to be mandatory for retroviruses, since Equine Infectious Anemia Virus (EIAV), an HIV cousin, has been predicted to have low PID level for the matrix; i.e. its matrix protein p15 contains only 21% PID residues. Surprisingly, the PID percentage and the pattern of predicted disorder distribution for p15 resemble those of the influenza matrix protein M1 (25%).

Conclusion: Our data might have important implications in the search for HIV vaccines since disorder in the matrix protein might provide a mechanism for immune evasion.

Figure 1

A bar chart comparing matrix proteins across virus types.

Figure 2

PONDR/B-factor plots of matrix proteins of various viruses A) the influenza A M1 protein B) the SIV_mac P17 protein. C) HIV-1 p17 Matrix protein D) The EIAV p15 Matrix protein. Protein-protein contacts between chains are annotated by thick gray horizontal spots. The normalized B-factor values are seen in the light gray curves. PONDR-VLXT scores are seen in the black curve in each plot.

Figure 3

The three dimensional structures of the matrix proteins of the various viruses with predicted disorder annotation by red and magenta colors. A) The influenza m1 protein B) SIVmac p17 Protein C) HIV-1 p17 protein shown as a monomer D) The EIAV p15 E) The HIV-1 p17 shown as a multimer. The regions in magenta are regions predicted to be disordered by VL3 (and probably also by VLXT). By contrast, the regions in red are areas predicted to be disordered by VLXT.

Figure 4

Schematic diagram: glycoconjugate acts as a broom with sweeping motion arising from matrix. The striped arrows depict the motions of oligosaccharides arising from the bobbing of the lipid bilayer. The motions of the membrane is also dependent on the matrix for stability or lack of it. The motions of the oligosaccharide may allow and prevent the binding of CD4 and antibodies respectively.