Structure of the adenosine-bound human adenosine A1 receptor-Gi complex.
Nature
; 558(7711): 559-563, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29925945
ABSTRACT
The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human A1R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A1R, 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 A1R primarily via amino acids in the C terminus of the Gαi α5-helix, concomitant with a 10.5 Å outward movement of the A1R transmembrane domain 6. Comparison with the agonist-bound ß2 adrenergic receptor-Gs-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A1R structure provides molecular insights into receptor and G-protein selectivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenosina
/
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
/
Microscopia Crioeletrônica
/
Receptor A1 de Adenosina
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article