5XF1

Structure of the Full-length glucagon class B G protein-coupled receptor

Summary for 5XF1

• Entry DOI: 10.2210/pdb5xf1/pdb
• Related: 5XEZ
• Related PRD ID: PRD_900017
• Descriptor: Glucagon receptor,Endolysin,Glucagon receptor, Antibody mAb1 Heavy chain, Antibody mAb1 Light chain, ... (8 entities in total)
• Functional Keywords: human gcgr receptor, class b, 7tm domain, membrane, lcp, xfel, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 232169.82

Authors

Zhang, H.,Qiao, A.,Yang, D.,Yang, L.,Dai, A.,de Graaf, C.,Reedtz-Runge, S.,Dharmarajan, V.,Zhang, H.,Han, G.W.,Grant, T.,Sierra, R.,Weierstall, U.,Nelson, G.,Liu, W.,Wu, Y.,Ma, L.,Cai, X.,Lin, G.,Wu, X.,Geng, Z.,Dong, Y.,Song, G.,Griffin, P.,Lau, J.,Cherezov, V.,Yang, H.,Hanson, M.,Stevens, R.,Jiang, H.,Wang, M.,Zhao, Q.,Wu, B. (deposition date: 2017-04-06, release date: 2017-05-24, Last modification date: 2024-11-20)

Primary citation

Zhang, H.,Qiao, A.,Yang, D.,Yang, L.,Dai, A.,de Graaf, C.,Reedtz-Runge, S.,Dharmarajan, V.,Zhang, H.,Han, G.W.,Grant, T.D.,Sierra, R.G.,Weierstall, U.,Nelson, G.,Liu, W.,Wu, Y.,Ma, L.,Cai, X.,Lin, G.,Wu, X.,Geng, Z.,Dong, Y.,Song, G.,Griffin, P.R.,Lau, J.,Cherezov, V.,Yang, H.,Hanson, M.A.,Stevens, R.C.,Zhao, Q.,Jiang, H.,Wang, M.W.,Wu, B.
Structure of the full-length glucagon class B G-protein-coupled receptor.
Nature, 546:259-264, 2017

PubMed Abstract: The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor 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 extracellular 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 extracellular loop exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.

PubMed: 28514451
DOI: 10.1038/nature22363

Experimental method

X-RAY DIFFRACTION (3.19 Å)