Systematic protein-protein interaction mapping for clinically relevant human GPCRs.
Mol Syst Biol
; 13(3): 918, 2017 03 15.
Article
em En
| MEDLINE
| ID: mdl-28298427
ABSTRACT
G-protein-coupled receptors (GPCRs) are the largest family of integral membrane receptors with key roles in regulating signaling pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR-mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two-hybrid (MYTH) approach and identified interacting partners for 48 selected full-length human ligand-unoccupied GPCRs in their native membrane environment. The resulting GPCR interactome connects 686 proteins by 987 unique interactions, including 299 membrane proteins involved in a diverse range of cellular functions. To demonstrate the biological relevance of the GPCR interactome, we validated novel interactions of the GPR37, serotonin 5-HT4d, and adenosine ADORA2A receptors. Our data represent the first large-scale interactome mapping for human GPCRs and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mapeamento de Interação de Proteínas
/
Receptores Acoplados a Proteínas G
/
Mapas de Interação de Proteínas
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article