5UZ7

Volta phase plate cryo-electron microscopy structure of a calcitonin receptor-heterotrimeric Gs protein complex

Summary for 5UZ7

• Entry DOI: 10.2210/pdb5uz7/pdb
• EMDB information: 8623
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, 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, ... (5 entities in total)
• Functional Keywords: class b g protein-coupled receptor agonist-receptor-g protein ternary complex calcitonin receptor active-state g protein-coupled receptor, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 164244.62

Authors

Liang, Y.L.,Khoshouei, M.,Radjainia, M.,Zhang, Y.,Glukhova, A.,Tarrasch, J.,Thal, D.M.,Furness, S.G.B.,Christopoulos, G.,Coudrat, T.,Danev, R.,Baumeister, W.,Miller, L.J.,Christopoulos, A.,Kobilka, B.K.,Wootten, D.,Skiniotis, G.,Sexton, P.M. (deposition date: 2017-02-24, release date: 2017-05-03, Last modification date: 2024-10-16)

Primary citation

Liang, Y.L.,Khoshouei, M.,Radjainia, M.,Zhang, Y.,Glukhova, A.,Tarrasch, J.,Thal, D.M.,Furness, S.G.B.,Christopoulos, G.,Coudrat, T.,Danev, R.,Baumeister, W.,Miller, L.J.,Christopoulos, A.,Kobilka, B.K.,Wootten, D.,Skiniotis, G.,Sexton, P.M.
Phase-plate cryo-EM structure of a class B GPCR-G-protein complex.
Nature, 546:118-123, 2017

PubMed Abstract: Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7. This conformation is accompanied by a 60° kink in helix 6 and a large outward movement of the intracellular end of this helix, opening the bundle to accommodate interactions with the α5-helix of Gα. Also observed is an extended intracellular helix 8 that contributes to both receptor stability and functional G-protein coupling via an interaction with the Gβ subunit. This structure provides a new framework for understanding G-protein-coupled receptor function.

PubMed: 28437792
DOI: 10.1038/nature22327

Experimental method

ELECTRON MICROSCOPY (4.1 Å)