6LML

Cryo-EM structure of the human glucagon receptor in complex with Gi1

Summary for 6LML

• Entry DOI: 10.2210/pdb6lml/pdb
• EMDB information: 0918
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: glucagon receptor, gpcr, gi1 protein, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 165415.06

Authors

Qiao, A.,Han, S.,Li, X.,Sun, F.,Zhao, Q.,Wu, B. (deposition date: 2019-12-26, release date: 2020-04-01, Last modification date: 2024-10-16)

Primary citation

Qiao, A.,Han, S.,Li, X.,Li, Z.,Zhao, P.,Dai, A.,Chang, R.,Tai, L.,Tan, Q.,Chu, X.,Ma, L.,Thorsen, T.S.,Reedtz-Runge, S.,Yang, D.,Wang, M.W.,Sexton, P.M.,Wootten, D.,Sun, F.,Zhao, Q.,Wu, B.
Structural basis of Gsand Girecognition by the human glucagon receptor.
Science, 367:1346-1352, 2020

PubMed Abstract: Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, G or G These two structures adopt a similar open binding cavity to accommodate G and G The G binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G more than G binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.

PubMed: 32193322
DOI: 10.1126/science.aaz5346

Experimental method

ELECTRON MICROSCOPY (3.9 Å)