Structural insights into GLP-1R and GIPR co-agonism

In order to investigate the molecular mechanism of co-agonism at two validated targets for varies metabolic diseases, the glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), 12 novel cryogenic transmission electron microscopy (cryo-EM) structures of GLP-1R:Gs protein or GIPR:Gs protein complexes bound to ligands of differing pharmacology were determined in this thesis. The results reveal how different agonists engage both receptors, and provide insights into how distinct profiles of pharmacology arise. My PhD thesis advances the understanding of co-agonism at the GLP-1R and GIPR.