Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
The adenosine A2A receptor (A2AR) is a prototypical G protein-coupled receptor (GPCR) that couples to the heterotrimeric G protein GS. Here we determine the structure by electron cryo-microscopy (cryo-EM) of A2AR at pH 7.5 bound to the small molecule agonist NECA and coupled to an engineered heterotrimeric G protein, which contains mini-GS, the βγ subunits and nanobody Nb35. Most regions of the complex have a resolution of ~3.8 Å or better. Comparison with the 3.4 Å resolution crystal structure shows that the receptor and mini-GS are virtually identical and that the density of the side chains and ligand are of comparable quality. However, the cryo-EM density map also indicates regions that are flexible in comparison to the crystal structures, which unexpectedly includes regions in the ligand binding pocket. In addition, an interaction between intracellular loop 1 of the receptor and the β subunit of the G protein was observed.
Data availability
Structural data have been deposited in the PDB under the accession code 6gdg and in EMDB with accession code 4390
Article and author information
Author details
Christopher G Tate
Funding
Medical Research Council (U105197215)
- Christopher G Tate
European Research Council (EMPSI 339995)
- Christopher G Tate
Heptares Therapeutics (n/a)
- Christopher G Tate
Pfizer UK (n/a)
- Christopher G Tate
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, García-Nafría et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein
eLife 7:e35946.
https://doi.org/10.7554/eLife.35946
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