Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein.
Elife
; 72018 05 04.
Article
em En
| MEDLINE
| ID: mdl-29726815
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 ßγ 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 ß subunit of the G protein was observed.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Heterotriméricas de Ligação ao GTP
/
Receptor A2A de Adenosina
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article