Crystal Structures of the Pro-Inflammatory Cytokine Interleukin-23 and Its Complex with a High-Affinity Neutralizing Antibody

Journal Article · Thu Jun 25 00:00:00 EDT 2009 · J. Mol. Biol.

DOI:https://doi.org/10.1016/j.jmb.2008.08.001· OSTI ID:1007103

Beyer, Brian M; Ingram, Richard; Ramanathan, Lata; Reichert, Paul; Le, Hung V; Madison, Vincent; Orth, Peter ^[1]

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1. SPRI

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 {angstrom}, 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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1007103
• Journal Information: J. Mol. Biol., Vol. 382, Issue (4) ; 10, 2008; ISSN 0022-2836
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DISEASES
LYMPHOKINES
PATHOGENESIS
RESIDUES