Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody.
J Mol Biol
; 382(4): 942-55, 2008 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-18708069
ABSTRACT
Interleukin (IL)-23 is a pro-inflammatory cytokine playing a key role in the pathogenesis of several autoimmune and inflammatory diseases. We have determined the crystal structures of the heterodimeric p19-p40 IL-23 and its complex with the Fab (antigen-binding fragment) of a neutralizing antibody at 2.9 and 1.9 A, respectively. The IL-23 structure closely resembles that of IL-12. They share the common p40 subunit, and IL-23 p19 overlaps well with IL-12 p35. Along the hydrophilic heterodimeric interface, fewer charged residues are involved for IL-23 compared with IL-12. The binding site of the Fab is located exclusively on the p19 subunit, and comparison with published cytokine-receptor structures suggests that it overlaps with the IL-23 receptor binding site.
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Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
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Fragmentos Fab das Imunoglobulinas
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Subunidade p40 da Interleucina-12
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Subunidade p19 da Interleucina-23
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Inflamação
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article