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CCeMMP Seminar Series – Prof. Patrick Sexton October 2021

Using cryo-EM to interrogate the structure and dynamics of GPCRs

G protein-coupled receptors (GPCRs) are the largest superfamily of cell surface receptor proteins and a major target class for drug development. GPCRs are inherently flexible proteins that have evolved to allosterically communicate external signals to modulation of cellular function through recruitment and activation of transducer proteins, particularly G proteins. Technological evolution in cryo-EM combined with continuing advances in biochemical approaches for the stabilisation of active-state complexes of GPCRs with different transducer proteins is now enabling structural interrogation of receptor activation and transducer engagement. Moreover, cryo-EM can access conformational ensembles of GPCR complexes that are present during vitrification, which can provide a window into the dynamics of these complexes.

Prof. Patrick Sexton

Director, ARC Centre for Cryo-electron Microscopy of Membrane Proteins; 

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University