Insights into the structure of class B GPCRs

• GCGR and CRF1 structures show different features compared to class A GPCRs.
• Class B structures and structure-based drug discovery for peptide hormone GPCRs.
• Glucagon, GLP1, and GIP peptide molecular recognition and diabetes.
• Corticotropin-releasing factor and stress.

The secretin-like (class B) family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis and are interesting drug targets for the treatment of several metabolic disorders (such as type 2 diabetes, osteoporosis, and obesity) and nervous system diseases (such as migraine, anxiety, and depression). The recently solved crystal structures of the transmembrane domains of the human glucagon receptor and human corticotropin-releasing factor receptor 1 have opened up new opportunities to study the structure and function of class B GPCRs. The current review shows how these structures offer more detailed explanations to previous biochemical and pharmacological studies of class B GPCRs, and provides new insights into their interactions with ligands.