Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, United States.
Cytokine Growth Factor Rev. 2010 Oct;21(5):325-30. doi: 10.1016/j.cytogfr.2010.08.003. Epub 2010 Sep 16.
Interleukin-10 (IL-10) family of cytokines includes a number of its viral homologs and eight cellular cytokines (IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29). The latter three proteins are also known as IFN-λ2, IFN-λ3, and IFN-λ1, and are recognized as type III (or λ) interferons. Most of the cellular homologs of IL-10 are monomeric in solution, whereas IL-10 and its viral homologs are intercalated dimers consisting of two helical bundle domains topologically similar to the monomeric members of the family. A classical four-helix bundle, a signature element of all helical cytokines, is always found as part of the domain of each member of the IL-10 family. The only crystal structures of these cytokine receptors that have been determined to date are for their extracellular domains (ECDs). Each ECD consists of two β-sandwich domains connected in the middle by a linkage. Signal transduction occurs when a cytokine binds to its two appropriate receptor chains. IL-10 and its viral homologs use the same IL-10 receptor system, whereas the cellular homologs of IL-10 use their own receptors, which in some cases may overlap and be used in different pairwise combinations. The known structures of binary complexes allowed for marking of the receptor binding site, which always includes helix A, loop AB and helix F (IL-10 notations) on the side of a ligand, loops of the N-terminal and C-terminal domains directed toward the ligand, and the interdomain linkage of the ECD. An analysis of the published structures of both the binary and ternary complexes of all helical cytokines allowed for the generation of a model of the signaling complex of IL-10. The receptor binding site I of the high affinity receptor IL-10R1 is exactly the same as in the crystal structure of the binary IL-10/sIL-10R1 complex, whereas the receptor binding site II is located on the surface of the first and the third helices of the four-helix bundle. The receptor/receptor interface, or site III, is formed between the C-terminal domains of IL-10R1 and IL-10R2.
白细胞介素-10（IL-10）家族细胞因子包括许多其病毒同系物和 8 种细胞因子（IL-19、IL-20、IL-22、IL-24、IL-26、IL-28A、IL-28B 和 IL-29）。后三种蛋白也被称为 IFN-λ2、IFN-λ3 和 IFN-λ1，被认为是 III 型（或 λ 型）干扰素。大多数 IL-10 的细胞同系物在溶液中为单体，而 IL-10 和其病毒同系物为嵌合二聚体，由拓扑结构类似于家族单体成员的两个螺旋束域组成。经典的四螺旋束是所有螺旋细胞因子的特征元素，总是作为 IL-10 家族每个成员的结构域的一部分发现。迄今为止，已经确定了这些细胞因子受体的唯一晶体结构是其细胞外结构域（ECD）。每个 ECD 由两个β-三明治结构域在中间通过连接连接。当细胞因子与两个适当的受体链结合时，就会发生信号转导。IL-10 和其病毒同系物使用相同的 IL-10 受体系统，而 IL-10 的细胞同系物使用其自身的受体，在某些情况下，这些受体可能重叠并以不同的配对组合使用。已知的二元复合物结构允许标记受体结合位点，该位点始终包括配体一侧的螺旋 A、AB 环和 F 螺旋（IL-10 标记）、N 端和 C 端结构域的环指向配体，以及 ECD 的结构域间连接。对所有螺旋细胞因子的已发表的二元和三元复合物结构的分析允许生成 IL-10 信号复合物的模型。高亲和力受体 IL-10R1 的受体结合位点 I 与晶体结构中的二元 IL-10/sIL-10R1 复合物完全相同，而受体结合位点 II 位于四螺旋束的第一和第三螺旋的表面。受体/受体界面或位点 III 是在 IL-10R1 和 IL-10R2 的 C 端结构域之间形成的。
