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  Phase-plate cryo-EM structure of a class B GPCR-G-protein complex

Liang, Y.-L., Khoshouei, M., Radjainia, M., Zhang, Y., Glukhova, A., Tarrasch, J., et al. (2017). Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. Nature, 546(7656), 118-123. doi:10.1038/nature22327.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-E145-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-E146-B
Genre: Journal Article

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 Creators:
Liang, Yi-Lynn1, Author
Khoshouei, Maryam2, Author              
Radjainia, Mazdak1, Author
Zhang, Yan1, Author
Glukhova, Alisa1, Author
Tarrasch, Jeffrey1, Author
Thal, David M.1, Author
Furness, Sebastian G. B.1, Author
Christopoulos, George1, Author
Coudrat, Thomas1, Author
Danev, Radostin2, Author              
Baumeister, Wolfgang2, Author              
Miller, Laurence J.1, Author
Christopoulos, Arthur1, Author
Kobilka, Brian K.1, Author
Wootten, Denise1, Author
Skiniotis, Georgios1, Author
Sexton, Patrick M.1, Author
Affiliations:
1external, ou_persistent22              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: PEPTIDE-1 RECEPTOR; SALMON-CALCITONIN; COUPLED RECEPTORS; GLUCAGON RECEPTOR; BIASED AGONISM; BINDING; ACTIVATION; PHARMACOLOGY; CONSEQUENCES; SPECIFICITYScience & Technology - Other Topics;
 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 G alpha(s)beta gamma 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 degrees kink in helix 6 and a large outward movement of the intracellular end of this helix, opening the bundle to accommodate interactions with the alpha 5-helix of G alpha(s). Also observed is an extended intracellular helix 8 that contributes to both receptor stability and functional G-protein coupling via an interaction with the G beta subunit. This structure provides a new framework for understanding G-protein-coupled receptor function.

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Language(s): eng - English
 Dates: 2017
 Publication Status: Published in print
 Pages: 18
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: ISI: 000402372800039
DOI: 10.1038/nature22327
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
 Creator(s):
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 546 (7656) Sequence Number: - Start / End Page: 118 - 123 Identifier: ISSN: 0028-0836
CoNE: /journals/resource/954925427238