Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site

被引:179
作者
Josephson, K
Logsdon, NJ
Walter, MR [1 ]
机构
[1] Univ Alabama Birmingham, Ctr Macromol Crystallog, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
关键词
D O I
10.1016/S1074-7613(01)00169-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). This intermediate complex must subsequently recruit the low-affinity IL-10R2 chain before cell signaling can occur. Here we report the 2.9 Angstrom crystal structure of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex consists of two IL-10s and four sIL-10R1 molecules. Several residues in the IL-10/sIL-10R1 interface are conserved in all IL-10 homologs and their receptors. The data suggests that formation of the active IL-10 signaling complex occurs by a novel molecular recognition paradigm where IL-10R1 and IL-10R2 both recognize the same binding site on IL-10.
引用
收藏
页码:35 / 46
页数:12
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