Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody

被引：50

作者：

Beyer, Brian M. ^{[1
]}

Ingram, Richard ^{[1
]}

Ramanathan, Lata ^{[1
]}

Reichert, Paul ^{[1
]}

Le, Hung V. ^{[1
]}

Madison, Vincent ^{[1
]}

Orth, Peter ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2008年 / 382卷 / 04期

关键词：

IL-23; cytokine; Fab; receptor; crystal structure;

D O I：

10.1016/j.jmb.2008.08.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：942 / 955

页数：14

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