Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR.
Cell
; 155(6): 1258-69, 2013 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-24290358
ABSTRACT
Molecular determinants regulating the activation of class B G-protein-coupled receptors (GPCRs) by native peptide agonists are largely unknown. We have investigated here the interaction between the corticotropin releasing factor receptor type 1 (CRF1R) and its native 40-mer peptide ligand Urocortin-I directly in mammalian cells. By incorporating unnatural amino acid photochemical and new click-chemical probes into the intact receptor expressed in the native membrane of live cells, 44 intermolecular spatial constraints have been derived for the ligand-receptor interaction. The data were analyzed in the context of the recently resolved crystal structure of CRF1R transmembrane domain and existing extracellular domain structures, yielding a complete conformational model for the peptide-receptor complex. Structural features of the receptor-ligand complex yield molecular insights on the mechanism of receptor activation and the basis for discrimination between agonist and antagonist function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Modelos Moleculares
/
Receptores de Hormônio Liberador da Corticotropina
/
Urocortinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article