Characterizing allosteric sites and conformational diversity of G-protein coupled receptors

  • Project Leader

    Associate Professor Paul Gooley
    T: +61 3 8344 2273
    E: prg@unimelb.edu.au
    W: Personal web page

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

Project Details

There is intense interest in G-protein coupled receptors (GPCRs) as they are the most important family of protein targets for drug design. GPCRs are dynamic, integral membrane molecules which have made them difficult to characterize.  By having a range of conformational states an individual GPCR can couple to a number of signaling pathways, however, a drug may turn on all these pathways which can lead to undesirable side effects. Additionally, the pathway of ligand-binding can include allosteric sites that can both influence selectivity of signaling pathways and be potential novel drug target sites. This project is therefore aimed at characterizing the dynamic states and allosteric sites of GPCRs and to finding compounds that are more specific and have promise as therapeutics. We work on several GPCRs: the neurotensin receptor, identified as a target for neurodegenerative diseases such as Schizophrenia and Parkinson’s; and the α1A-and α1B-adrenoreceptor which are important in cardiac and neuroprotection. Dr Daniel Scott has developed an innovative method of stabilizing GPCRs in detergent systems which importantly results in milligram amounts of stable receptor for biophysical characterization of both the unbound and bound states. This development gives a powerful resource for understanding GPCR mechanism. We are developing methods to rapidly determine if sets of ligands bind to the same site, have similar orientations, and show subtype specificity.

scheme showing restricted conformation of adrenaline

Research Group

Gooley laboratory: Structural biology of disease



Faculty Research Themes

Neuroscience

School Research Themes

Biomedical Neuroscience, 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