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initiate SMOOTHENED-PKA signaling in the Hedgehog cascade Elita Yuliantie , Arthur Christopoulos , Patrick M. Sexton , Denise Wootten , et al., for their work on Isoquinoline small molecule ligands are agonists

Molecular insights into G protein coupling specificity at a class A GPCR Jianjun Cao, Arthur Christopoulos, Patrick M. Sexton et al. for their job on Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP

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

Patrick Sexton Dr. GPCR Podcast << Back to podcast list Dr. Patrick Sexton !

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

Patrick Giguère Dr. Patrick Giguère Dr.