EMD-8623
Volta phase plate cryo-electron microscopy structure of a calcitonin receptor-heterotrimeric Gs protein complex
EMD-8623
Single-particle4.1 Å

Map released: 03/05/2017
Last modified: 16/10/2024
Sample Organism:
Homo sapiens,
Lama Glama
Sample: Complex of a full-length, active-state calcitonin receptor with peptide ligand, heterotrimeric Gs protein and nano body 35.
Fitted models: 5uz7 (Avg. Q-score: 0.413)
Deposition Authors: Liang YL, Khoshouei M
Sample: Complex of a full-length, active-state calcitonin receptor with peptide ligand, heterotrimeric Gs protein and nano body 35.
Fitted models: 5uz7 (Avg. Q-score: 0.413)
Deposition Authors: Liang YL, Khoshouei M
Phase-plate cryo-EM structure of a class B GPCR-G-protein complex.
Liang YL,
Khoshouei M,
Radjainia M,
Zhang Y
,
Glukhova A
,
Tarrasch J,
Thal DM
,
Furness SGB
,
Christopoulos G,
Coudrat T
,
Danev R,
Baumeister W,
Miller LJ,
Christopoulos A,
Kobilka BK
,
Wootten D
,
Skiniotis G
,
Sexton PM
(2017) Nature , 546 , 118 - 123









(2017) Nature , 546 , 118 - 123
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 Gαsβγ 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 Gαs. 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.
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 Gαsβγ 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 Gαs. 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.