Title : Structure of the full-length
glucagon class B
G-protein-coupled
receptor
Abstract :
- The human glucagon receptor , GCGR , belongs to the class B G-protein-coupled receptor r family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes
- Here we report the 3.0 Å crystal structure of full-length GCGR containing both the extracellula r domain and transmembrane domain in an inactive conformation
- The two domains are connected by a 12-residue segment termed the stalk, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain
- The first extracellula r loop exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure
- Hydrogen-deuterium exchange, disulfide crosslinking and molecula r dynamics studies suggest that the stalk and the first extracellula r loop have critical roles in modulating peptide ligand binding and receptor activation
- These insights into the full-length GCGR structure deepen ou r understanding of the signalling mechanisms of class B G-protein-coupled receptors