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Structure of the adenosine A2A receptor bound to an engineered G protein
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Carpenter, Byron, Nehmé, Rony, Warne, Tony, Leslie, Andrew G. W. and Tate, Christopher G. (2016) Structure of the adenosine A2A receptor bound to an engineered G protein. Nature, 536 (7614). pp. 104-107. doi:10.1038/nature18966 ISSN 0028-0836.
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Official URL: http://dx.doi.org/10.1038/nature18966
Abstract
G-protein-coupled receptors (GPCRs) are essential components of the signalling network throughout the body. To understand the molecular mechanism of G-protein-mediated signalling, solved structures of receptors in inactive conformations and in the active conformation coupled to a G protein are necessary1, 2. Here we present the structure of the adenosine A2A receptor (A2AR) bound to an engineered G protein, mini-Gs, at 3.4 Å resolution. Mini-Gs binds to A2AR through an extensive interface (1,048 Å2) that is similar, but not identical, to the interface between Gs and the β2-adrenergic receptor3. The transition of the receptor from an agonist-bound active-intermediate state4, 5 to an active G-protein-bound state is characterized by a 14 Å shift of the cytoplasmic end of transmembrane helix 6 (H6) away from the receptor core, slight changes in the positions of the cytoplasmic ends of H5 and H7 and rotamer changes of the amino acid side chains Arg3.50, Tyr5.58 and Tyr7.53. There are no substantial differences in the extracellular half of the receptor around the ligand binding pocket. The A2AR–mini-Gs structure highlights both the diversity and similarity in G-protein coupling to GPCRs6 and hints at the potential complexity of the molecular basis for G-protein specificity.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Journal or Publication Title: | Nature | ||||||||
Publisher: | Nature Publishing | ||||||||
ISSN: | 0028-0836 | ||||||||
Official Date: | 27 July 2016 | ||||||||
Dates: |
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Volume: | 536 | ||||||||
Number: | 7614 | ||||||||
Page Range: | pp. 104-107 | ||||||||
DOI: | 10.1038/nature18966 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Open Access Version: |
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