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Nayara Braga Emidio, Ross Cheloha, Laura M Wingler, et al. for their work on Nanobody-Mediated Dualsteric

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. Different agonists can promote differential receptor-induced signaling responses - termed bias - potentially by eliciting different levels of recruitment of effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias is difficult. Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well as arrestin3 binding to the muscarinic acetylcholine receptor M3 by utilizing FRET-based assays. In order to avoid interference between these interactions, we studied GRK2 binding in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation influencing arrestin recruitment. We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 interaction. However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements for arrestin3 binding to M3R are distinct. Read full article

Vlaams Instituut Biotechnologie, at the Vrije Universiteit Brusle, Brussels, Belgium, has been named the winner

Lauren M. Slosky Dr. GPCR Podcast << Back to podcast list Dr. Lauren M. Slosky About Dr. Lauren M. Lauren M.

Laura Bohn’s lab at Scripps Research Institute in Florida.

Laura Bohn (1999) Dr. Kathleen Caron - Co-host- (1970) Dr. Henrik Dohlman (1987) Dr.