The role of the rabies P protein in evading the interferon-mediated pathway

  • Project Leader

    Associate Professor Paul Gooley
    T: +61 3 8344 2273
    W: Personal web page

    Location: 402, Level 04, Bio21 Institute, 30 Flemington Rd, Parkville

Project Details

The rabies virus  phosphoprotein (P protein) has a central role in the neutralization of host innate defences by acting to antagonize type I interferon (IFN), thereby preventing both transcriptional induction of IFN and expression of IFN-stimulated genes in target cells. Specifically, rabies P protein inhibits IFN-α and IFN-γ mediated transcriptional responses and subsequently prevents nuclear accumulation of the signal transducer and activator of transcription 1 (STAT1α) to overcome an antiviral state of the infected cells. Recently a hydrophobic pocket of the P protein C-terminal domain has been identified as a critical interacting site for STAT1α binding. To obtain insight into the mechanism by which P-protein interacts with STAT1α, this project aims to determine the interacting residues/sites of the C-terminal domain of P protein and STAT1α. We can express and purify both proteins but STAT1α is a large protein making traditional biophysical studies complicated. This project will therefore use novel structural biology approaches, including paramagnetic labelling of STAT1α, to probe and define this interaction. Part of the aim of this work is to develop novel ligands that interfere or simulate the way P-protein interacts with STAT1α. Towards this goal we have identified a part of the rabies N-protein and how it binds to P-protein. We will use this peptide and engage in a synthetic program to design new peptides with higher affinity and use these to probe in vivo P-protein interactions.

Research Group

Gooley laboratory: Structural biology of disease

Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease, Cellular Imaging & Structural Biology

Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Biochemistry and Molecular Biology

Unit / Centre

Gooley laboratory: Structural biology of disease