白细胞介素-10/白细胞介素-10受体1复合物的晶体结构揭示了一个共享的受体结合位点。

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

作者信息

Josephson K, Logsdon N J, Walter M R

机构信息

Center for Macromolecular Crystallography, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

出版信息

Immunity. 2001 Jul;15(1):35-46. doi: 10.1016/s1074-7613(01)00169-8.

DOI:10.1016/s1074-7613(01)00169-8

PMID:11485736

Abstract

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 A 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.

摘要

白细胞介素10（IL-10）是一种二聚体细胞因子，在抑制炎症反应中起核心作用。这些活性依赖于IL-10与其高亲和力受体（IL-10R1）的相互作用。在细胞信号传导发生之前，这个中间复合物必须随后招募低亲和力的IL-10R2链。在此，我们报道了与可溶性形式的IL-10R1（sIL-10R1）结合的IL-10的2.9埃晶体结构。该复合物由两个IL-10和四个sIL-10R1分子组成。IL-10 / sIL-10R1界面中的几个残基在所有IL-10同源物及其受体中都是保守的。数据表明，活性IL-10信号复合物的形成是通过一种新的分子识别模式发生的，其中IL-10R1和IL-10R2都识别IL-10上的相同结合位点。