Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1 beta
Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1 beta
复制标题
DOI：
10.1038/386190a0
复制
发表时间：
1997-03-13
期刊：
影响因子：
64.8
通讯作者：
Brandhuber, BJ
中科院分区：
文献类型：
--
作者：
Vigers, GPA;Anderson, LJ;Brandhuber, BJ
白细胞介素-1 （IL-1）是炎症性疾病的重要介质。IL-1家族目前包括两种激动剂，IL-1 α和IL-1 β，以及一种拮抗剂IL-1ra。这些分子中的每一个都与I型IL-1受体（IL1R）结合(1)。IL-1 α或IL-1 β与il - 1r的结合是IL-1信号转导的早期步骤，因此阻断这种相互作用可能是开发新药的有用靶点。在这里，我们报道了IL-1 β与il - 1r细胞外结构域（s-IL1R）结合的三维结构，分辨率为2.5埃。IL-1 β以1:1的化学计量与s- il - 1r结合。晶体结构表明s-IL1R由三个免疫球蛋白样结构域组成，这些结构域以不同于先前描述的细胞因子受体复合物的结构包裹着IL-1 β。通过位点定向诱变（2,3）鉴定的IL-1 β上的两个受体结合区域都与受体接触：一个结合受体的前两个结构域，而另一个只结合受体的第三个结构域。
Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1 alpha and IL-1 beta, and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R)(1). The binding of IL-1 alpha or IL-1 beta to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs, Here we report the three-dimensional structure of IL-1 beta bound to the extracellular domain of IL1R (s-IL1R) at 2.5 Angstrom resolution. IL-1 beta binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1 beta in a manner distinct from the structures of previously described cytokine-receptor complexes. The two receptor-binding regions on IL-1 beta identified by site-directed mutagenesis(2,3) both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.