Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like architecture for IL-5Rα.
Structure
; 19(12): 1864-75, 2011 Dec 07.
Article
en En
| MEDLINE
| ID: mdl-22153509
Interleukin-5 (IL-5) is the key mediator for the function of eosinophil granulocytes, whose deregulation is characteristic of hypereosinophilic diseases and presumably contributes to allergic asthma. IL-5 signaling involves two transmembrane receptors, IL-5Rα and the common ß chain, which upon formation of the ternary complex activate the JAK/STAT signaling cascade. To investigate the mechanism underlying ligand-receptor recognition, we determined the structure of IL-5 bound to the extracellular domain of IL-5Rα. IL-5 makes contact with all three fibronectin III-like domains of IL-5Rα, with the receptor architecture resembling a wrench. Mutagenesis data provide evidence that this wrench-like architecture is likely preformed. The structure demonstrates that for steric reasons, homodimeric IL-5 can bind only one receptor molecule, even though two equivalent receptor-binding sites exist. In regard to strong efforts being made to develop IL-5 antagonists for treating asthma and hypereosinophilic diseases, the advances in molecular understanding provided by this structure are of greatest value.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-5
/
Subunidad alfa del Receptor de Interleucina-5
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos