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IL-6受体结构与功能的研究进展 总被引:1,自引:0,他引:1
IL-6是一个多功能的细胞因子,其生物学作用在很大程度上受IL-6受体(IL-6R)结构和功能的影响。IL-6R由两条多肽链组成,即配体结合链gp80和信号传导链gp130。它们在结构和功能上既有分工又有合作。两种亚基组成的高和力IL-6R是介导细胞效应所必需的。IL-6Rα中的造血功能区属于造血因子受体超家族成员,它决定着结合IL-6的能力,然而gp130则是多种细胞因子共用的信号传递分子,其胞 相似文献
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任蕴芳 《中国应用生理学杂志》1992,8(4):373-376
白细胞介素6(IL-6)是一种具有广泛生物学功能的细胞因子,调节多种组织细胞的生长和分化,在免疫反应、急相反应和造血过程中起重要作用。IL-6对多种细胞的生物学效应是通过IL-6与细胞表面的IL-6受体结合并起动细胞内信号通路而介导的。本文从以下几个方面对近几年来有关IL-6受体研究的进展进行简要综述。 相似文献
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人IL-6受体是一个在各种细胞上广泛表达的跨膜糖蛋白分子,是IL-6发挥细胞效应所必需的。本文通过将IL-6RcDNA重组到痘苗病毒的TK基因中构建成重组痘苗病毒VIL6R。细胞原位杂交和APAAP染色结果表明,感染VIL6R后的Vero细胞中,IL-6R在mRNA和蛋白水平上均呈现较强的表达。Westernblot分析所表达的分子量为80kD,表明所表达的产物是糖基化的。IL-6结合试验表明,表达的膜IL-6R能够结合rIL-6,说明它是有功能的。利用VIL6R免疫小鼠后,能够刺激较强的抗体产生。从而为进一步研究IL-6R的信号传导和构效关系提供了基础。 相似文献
4.
Based on the spatial conformations of human interleukin-6 (hlL-6) derived from nuclear magnetic resonance analysis and human interleukin-6 receptor (hlL-6R) modeled with homology modeling method using human growth hormone receptor as template, the interaction between hlL-6 and its receptor (hIL-6R) is studied with docking program according to the surface electrostatic potential analysis and spatial conformation complement. The stable region structure composed of hlL-6 and hlL-6R is obtained on the basis of molecular mechanism optimization and molecular dynamics simulation. The binding domain between hIL-6 and hIL-6R is predicted theoretically. Furthermore, the especial binding sites that influence the interaction between hlL-6 and hlL-6R are confirmed. The results lay a theoretical foundation for confirming the active regions of hlL-6 and designing novel antagonist with computer-guided techniques. 相似文献
5.
hIL-6·hIL-6Rα·gp130三元复合物的结构预测 总被引:1,自引:0,他引:1
通过Delphi方法分析人白介素6(human interleukin-6,hIL-6)/人白介素6受体α亚基(human interleukin-6 receptor α subunit,hIL-6Rα)复合物、gp130(βsubunit)的空间构象的表现静电分布,利用分子对接方法研究gp130和hIL-6/hIL-6Rα复合物作用成三元复合物的空间构象,经过分子力学优化、分子动力学常温动态模 相似文献
6.
Three-dimensional structure and function study on the active region in the extracellular ligand-binding domain of human IL-6 receptor 总被引:1,自引:0,他引:1
In this study the three-dimensional (3-D) model of the ligand-binding domain (V106-P322) of human interleukin-6 receptor (hlL-6 R) was constructed by computer-guided ho-mology modeling technique using the crystal structure of the ligand-binding domain (K52-L251) of human growth hormone receptor (hGHR) as templet. Furthermore, the active binding region of the 3-D model of hlL-6R with the ligand (hlL-6) was predicted. In light of the structural characteristics of the active region, a hydrophobic pocket shielded by two hydrophilic residues (E115 and E505) of the region was identified by a combination of molecular modelling and the site-directed or double-site mutation of the twelve crucial residues in the ligand-binding domain of hIL-6R (V106-P322). We observed and analyzed the effects of these mutants on the spatial conformation of the pocket-like region of hlL-6 R. The results indicated that any site-directed mutation of the five Cys residues (four conservative Cys residues: Cyst 21, Cys132, Cys165, Cys1 相似文献
7.
人白介素6受体胞外区三维结构的同源模拟 总被引:1,自引:0,他引:1
IL-6受体是造血因子超家族成员,其胞外区细胞因子结合结构域(CBD)是受体结合配基和偶联gp130转导IL-6信号的功能域.据预测,IL-6R功能域的β片层折叠模式和人生长激素受体(hGH-R)及CD4的晶体结构十分相似.应用计算机同源模拟技术,以hGH-R和CD4的三维结构为模板,模建了hIL-6R功能域(106~322位)的三维结构,初步描述了其结构保守区的构象特征.文章研究模建的hIL-6R三维结构模式为探讨可溶性IL-6R点突变的结果,以及进行三维定量分析IL-6R胞外区功能域的构效关系提供了空间结构基础. 相似文献
8.
淋巴因子激活的杀伤细胞(LAK细胞)能广泛杀伤自身肿瘤、同种异体肿瘤。LAK细胞用于恶性肿瘤的过继免疫治疗是近年十分活跃的研究领域。IL—6是一种多功能细胞因子,在机体免疫系统、防御功能及造血调节中有重要作用。已有文献报道,IL—6可诱导IL—2受体表达,提高PHA刺激的细胞毒T细胞(CTL) 的杀瘤活性。本实验观察了IL—6和IL—2合用对人LAK细胞诱导及其杀瘤活性的影响。(1)在诱导LAK细胞克隆的含 相似文献
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荷兰应用科学研究院放射生物学研究所建立的可移植性大鼠急性白血病(brown Norway rat acutemyelocytic leukemia,BNML)是研究人急性粒系白血病的颇为完备的实验模型。由于重组人白细胞介素-6(rhIL-6)可作用于大鼠,然而大鼠BNML细胞系LT12缺乏rhIL-6受体(rhIL—6R)表达。为了在BNML模型上探讨rhIL-6在体外以及体内对白血病细胞增殖和分化的影响,并探讨细胞因子-毒素联接物用于白血病靶向治疗的可能性,本研究应用改良的磷酸钙共沉淀法将携带rhIL-6R cDNA的逆转录病毒表达质粒XM6/IL—6RNeo导入LT12细胞,经过G418筛选获得G418抗性克隆,建立了表达rhIL—6R的LT12亚细胞 相似文献
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