An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation.
Nat Struct Biol
; 5(11): 993-1004, 1998 Nov.
Article
en En
| MEDLINE
| ID: mdl-9808045
ABSTRACT
Dimerization of the erythropoietin (EPO) receptor (EPOR), in the presence of either natural (EPO) or synthetic (EPO-mimetic peptides, EMPs) ligands is the principal extracellular event that leads to receptor activation. The crystal structure of the extracellular domain of EPOR bound to an inactive (antagonist) peptide at 2.7 A resolution has unexpectedly revealed that dimerization still occurs, but the orientation between receptor molecules is altered relative to active (agonist) peptide complexes. Comparison of the biological properties of agonist and antagonist EMPs with EPO suggests that the extracellular domain orientation is tightly coupled to the cytoplasmic signaling events and, hence, provides valuable new insights into the design of synthetic ligands for EPOR and other cytokine receptors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
/
Transducción de Señal
/
Eritropoyetina
/
Receptores de Eritropoyetina
/
Proteínas de la Leche
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Struct Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos