How the outer part of GLP-1 receptors influences selective activation by different drugs

A total of 126 mutations were examined to study the biased agonism of the glucagon-like peptide-1 receptor (GLP-1R).

• Several mutations selectively abolished the recruitment of a protein called β-arrestin while still allowing for the production of another signaling molecule, cAMP.
• The extracellular domain (ECD) of GLP-1R is implicated in mediating biased signaling outcomes.
• Correlations were identified between specific sequence features of GLP-1R mutations and their functional signaling impacts.
• These findings contribute to understanding the mechanisms of biased agonism in G protein-coupled receptors (GPCRs).
• Insights gained may aid in the design of more effective and selective GLP-1R agonists.

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