Structural insights into differences in G protein activation by family A and family B GPCRs.
Science
; 369(6503)2020 07 31.
Article
de En
| MEDLINE
| ID: mdl-32732395
ABSTRACT
Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play important roles in carbohydrate metabolism. Recent structures of family B GPCR-Gs protein complexes reveal a disruption in the α-helix of transmembrane segment 6 (TM6) not observed in family A GPCRs. To investigate the functional impact of this structural difference, we compared the structure and function of the glucagon receptor (GCGR; family B) with the ß2 adrenergic receptor (ß2AR; family A). We determined the structure of the GCGR-Gs complex by means of cryo-electron microscopy at 3.1-angstrom resolution. This structure shows the distinct break in TM6. Guanosine triphosphate (GTP) turnover, guanosine diphosphate release, GTP binding, and G protein dissociation studies revealed much slower rates for G protein activation by the GCGR compared with the ß2AR. Fluorescence and double electron-electron resonance studies suggest that this difference is due to the inability of agonist alone to induce a detectable outward movement of the cytoplasmic end of TM6.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Récepteurs au glucagon
/
Récepteurs bêta-2 adrénergiques
/
Sous-unités alpha Gs des protéines G
Limites:
Humans
Langue:
En
Journal:
Science
Année:
2020
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique