Structural highlights
Function
[GLP1R_HUMAN] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Publication Abstract from PubMed
Glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor that plays an important role in glucose homeostasis and treatment of type 2 diabetes. Structures of full-length class B receptors were determined in complex with their orthosteric agonist peptides, however, little is known about their extracellular domain (ECD) conformations in the absence of orthosteric ligands, which has limited our understanding of their activation mechanism. Here, we report the 3.2 A resolution, peptide-free crystal structure of the full-length human GLP-1R in an inactive state, which reveals a unique closed conformation of the ECD. Disulfide cross-linking validates the physiological relevance of the closed conformation, while electron microscopy (EM) and molecular dynamic (MD) simulations suggest a large degree of conformational dynamics of ECD that is necessary for binding GLP-1. Our inactive structure represents a snapshot of the peptide-free GLP-1R and provides insights into the activation pathway of this receptor family.
Full-length human GLP-1 receptor structure without orthosteric ligands.,Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, Ren Q, Roed NK, Lin G, Hanson MA, Jiang H, Wang MW, Reedtz-Runge S, Song G, Stevens RC Nat Commun. 2020 Mar 9;11(1):1272. doi: 10.1038/s41467-020-14934-5. PMID:32152292[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, Ren Q, Roed NK, Lin G, Hanson MA, Jiang H, Wang MW, Reedtz-Runge S, Song G, Stevens RC. Full-length human GLP-1 receptor structure without orthosteric ligands. Nat Commun. 2020 Mar 9;11(1):1272. doi: 10.1038/s41467-020-14934-5. PMID:32152292 doi:http://dx.doi.org/10.1038/s41467-020-14934-5
