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  Structure of the adenosine-bound human adenosine A(1) receptor-G(i) complex

Draper-Joyce, C. J., Khoshouei, M., Thal, D. M., Liang, Y.-L., Nguyen, A. T. N., Furness, S. G. B., et al. (2018). Structure of the adenosine-bound human adenosine A(1) receptor-G(i) complex. Nature, 558(7711), 559-563. doi:10.1038/s41586-018-0236-6.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-70F0-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-70F1-F
Genre: Journal Article

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 Creators:
Draper-Joyce, Christopher J.1, Author
Khoshouei, Maryam2, Author              
Thal, David M.1, Author
Liang, Yi-Lynn1, Author
Nguyen, Anh T. N.1, Author
Furness, Sebastian G. B.1, Author
Venugopal, Hariprasad1, Author
Baltos, Jo-Anne1, Author
Plitzko, Jürgen M.2, Author              
Danev, Radostin2, Author              
Baumeister, Wolfgang2, Author              
May, Lauren T.1, Author
Wootten, Denise1, Author
Sexton, Patrick M.1, Author
Glukhova, Alisa1, Author
Christopoulos, Arthur1, 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: CRYO-EM STRUCTURE; PROTEIN-COUPLED RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTOR; STABILIZED ACTIVE STATE; VOLTA PHASE PLATE; CRYSTAL-STRUCTURE; OPIOID RECEPTOR; CRYOELECTRON MICROSCOPY; ADRENERGIC-RECEPTOR; ELECTRON-MICROSCOPYScience & Technology - Other Topics;
 Abstract: The class A adenosine A(1) receptor (A(1)R) is a G-protein-coupled receptor that preferentially couples to inhibitory G(i/o) heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 angstrom structure of the human A(1)R in complex with adenosine and heterotrimeric G(i2) protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A(1)R, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the A(1)R primarily via amino acids in the C terminus of the G alpha(i) alpha 5-helix, concomitant with a 10.5 angstrom outward movement of the A(1)R transmembrane domain 6. Comparison with the agonist-bound beta(2) adrenergic receptor G(s)-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A(1)R structure provides molecular insights into receptor and G-protein selectivity.

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Language(s): eng - English
 Dates: 2018-062018
 Publication Status: Published in print
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000436594300054
DOI: 10.1038/s41586-018-0236-6
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 558 (7711) Sequence Number: - Start / End Page: 559 - 563 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238