摘要
白细胞介素18(interleukin-18,IL-18)是IL-1家族中一种重要的细胞因子,在增强免疫、抗肿瘤等方面具有潜在应用价值。鸡IL-18(chicken interleukin-18,chIL-18)的cDNA于2000年被克隆,后续研究证明鸡IL-18与哺乳动物IL-18具有类似的生物学功能。IL-18可与靶细胞上的IL-18受体(IL-18R,包括IL-18Rα和IL-18Rβ)特异性结合形成受体复合物,介导细胞膜上的信号从胞外向胞内传递。作者在大肠杆菌中成功表达和纯化了chIL-18,利用昆虫细胞表达系统获得了chIL-18Rα和chIL-18Rβ的胞外结构域;他们还在体外重组并纯化了chIL-18/18Rα二元复合物与chIL-18/18Rα/18Rβ三元复合物,并生长出二元复合物晶体。这些工作为进一步测定chIL-18与其受体复合物的晶体结构,从而深入探讨chIL-18信号转导机制奠定了基础。
Interleukin-18（IL-18） is a member of the IL-1 family,which plays important roles in host immune response and regulation.Chicken IL-18（chIL-18） was cloned in 2000,and the subsequent studies showed that it had similar biological functions with mammalian IL-18.The biological activities of IL-18 are mediated by its receptors（IL-18R,including IL-18Rα and IL-18Rβ） expressed on the surface of target cells.The binding of IL-18 with IL-18Rα and IL-18Rβ forms a stable ligand-receptor complex,which subsequently activates intracellular signal transduction molecules.The authors expressed and purified mature chIL-18 with prokaryotic expression system and also obtained the extracellular domains of IL-18Rα and IL-18Rβ with insect cell expression system.They then reconstituted and purified the binary complex chIL-18 with chIL-18Rα and the ternary complex of chIL-18 with chIL-18Rα and chIL-18Rβ in vitro.They also successfully grew the crystals of chIL-18/18Rα binary complex and collected a diffraction dataset of 3 resolution.These results lay a strong basis for future structural studies of chIL-18 with its receptors,which would help better understanding of chIL-18 signal transduction.
出处
《生物物理学报》
CAS
CSCD
北大核心
2013年第5期327-337,共11页
Acta Biophysica Sinica
基金
"973"计划项目(2011CB910502)~~
