IL-1 Family Cytokines Use Distinct Molecular Mechanisms to Signal through Their Shared Co-receptor.
Immunity
; 47(3): 510-523.e4, 2017 09 19.
Article
en En
| MEDLINE
| ID: mdl-28930661
ABSTRACT
Within the interleukin 1 (IL-1) cytokine family, IL-1 receptor accessory protein (IL-1RAcP) is the co-receptor for eight receptor-cytokine pairs, including those involving cytokines IL-1ß and IL-33. Unlike IL-1ß, IL-33 does not have a signaling complex that includes both its cognate receptor, ST2, and the shared co-receptor IL-1RAcP, which we now present here. Although the IL-1ß and IL-33 complexes shared structural features and engaged identical molecular surfaces of IL-1RAcP, these cytokines had starkly different strategies for co-receptor engagement and signal activation. Our data suggest that IL-1ß binds to IL-1RI to properly present the cytokine to IL-1RAcP, whereas IL-33 binds to ST2 in order to conformationally constrain the cognate receptor in an IL-1RAcP-receptive state. These findings indicate that members of the IL-1 family of cytokines use distinct molecular mechanisms to signal through their shared co-receptor, and they provide the foundation from which to design new therapies to target IL-33 signaling.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Interleucina-1
/
Receptores de Interleucina-1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article