Franziska M Heydenreich, Michel Bouvier, Brian Kobilka, M Madan Babu, and their team's work on Molecular

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

Magdalena M Scharf, Antonella Di Pizio, Ines Liebscher, Hannes Schihada, and Gunnar Schulte et al. on Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, Cesare Orlandi and Michel Bouvier.

GPCR Symposia 2024: March 15th - GPCR Activation and Signaling Confirmed speakers include Drs: Franziska Heydenreich Sudarshan Rajagopal Graham Ladds Michel Bouvier June 07th - S tructural and Molecular Insights

.: Franziska Heydentrich - 8:00 AM EST Graham Ladds - 8:30 AM EST Sudarshan Rajagopal - 10:00 AM EST

Lauren M. Slosky About Dr. Lauren M. Lauren M.