6LN2

Crystal structure of full length human GLP1 receptor in complex with Fab fragment (Fab7F38)

Summary for 6LN2

• Entry DOI: 10.2210/pdb6ln2/pdb
• Descriptor: Glucagon-like peptide 1 receptor,Rubredoxin,Glucagon-like peptide 1 receptor, Fab7F38_light chain, Fab7F38_heavy chain, ... (6 entities in total)
• Functional Keywords: full length human glp1 receptor, class b, fab7f38, tmd, nam pf06372222, membrane protein, lcp
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 103206.35

Authors

Wu, F.,Yang, L.,Hang, K.,Laursen, M.,Wu, L.,Han, G.W.,Ren, Q.,Roed, N.K.,Lin, G.,Hanson, M.,Jiang, H.,Wang, M.,Reedtz-Runge, S.,Song, G.,Stevens, R.C. (deposition date: 2019-12-28, release date: 2020-03-18, Last modification date: 2023-11-22)

Primary citation

Wu, F.,Yang, L.,Hang, K.,Laursen, M.,Wu, L.,Han, G.W.,Ren, Q.,Roed, N.K.,Lin, G.,Hanson, M.A.,Jiang, H.,Wang, M.W.,Reedtz-Runge, S.,Song, G.,Stevens, R.C.
Full-length human GLP-1 receptor structure without orthosteric ligands.
Nat Commun, 11:1272-1272, 2020

PubMed Abstract: 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 Å 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.

PubMed: 32152292
DOI: 10.1038/s41467-020-14934-5

Experimental method

X-RAY DIFFRACTION (3.2 Å)