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Elife. 2018 May 4;7. pii: e35946. doi: 10.7554/eLife.35946.

Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein.

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MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Contributed equally


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.


G protein-coupled receptor; GPCR; adenosine receptors; biochemistry; chemical biology; mini-G protein; molecular biophysics; none; structural biology; structure

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