人甘露聚糖结合凝集素糖识别域对病原体的直接效应研究

发布时间：2018-01-05 01:23

本文关键词：人甘露聚糖结合凝集素糖识别域对病原体的直接效应研究　出处：《第一军医大学》2005年硕士论文　论文类型：学位论文

【摘要】：甘露聚糖结合凝集素(Mannan binding lectin,MBL)为肝细胞分泌的一种血清糖蛋白,属于C型凝集素超家族中胶凝素家族的成员,是天然免疫系统中重要的模式识别分子。成熟MBL肽链自N端至C端依次有富含Cys的N端区、胶原样区(collagen-like region,CLR)、颈区和C端糖识别域(Carbohydrate-recognition domain,CRD)。MBL在机体抗感染天然免疫中起重要作用。它利用CRD选择性识别和结合多种病原体表面以D-甘露糖、N-乙酰葡糖胺、N-乙酰甘露糖胺、N-乙酰半乳糖胺、岩藻糖等为末端糖基的糖结构。已发现CRD能识别和结合细菌、病毒、酵母、利什曼原虫等一系列病原体。MBL又籍其CLR经由凝集素途径激活补体系统,发挥溶菌或间接调理吞噬功能;还能与吞噬细胞表面的胶凝素受体(即Clq受体)结合,起直接调理作用。目前,关于MBL分子CRD的研究,生化学家着眼于其糖识别的分子机制,免疫学家则集中于CRD的微生物识别谱,而没有考虑CRD是否还有其它功能。近年来有研究提示,MBL能抑制流感病毒感染细胞,且这一作用不依赖补体;MBL还能干扰病毒粘附到宿主细胞,影响病毒的传播和释放。但未对这种作用与MBL结构的关系进行研究。我们认为,也许正如抗体的Fab片段除了识别抗原外还有中和毒素、中和病毒作用一样,MBL的CRD特别是具有较高亲和力的寡聚CRD可能具有中和病毒及阻抑细菌粘附等直接效应功能。为了探索上述可能性,本研究中,我们将MBL-CRD基因在大肠杆菌系统中进行表达,获得纯化的重组CRD多聚体蛋白,在对其配体结合活性进行分析的基础上,初步研究了MBL-CRD对病原体的直接效应。
[Abstract]:Mannan binding agglutinin (Mannan binding) is a serum glycoprotein secreted by hepatocytes. A member of the C-type lectin superfamily, it is an important pattern recognition molecule in the innate immune system. Mature MBL peptide chain has N-terminal region rich in Cys from N-terminal to C-terminal. Collagen-like region CLR. The cervical and C-terminal sugar recognition domains are Carbohydrate-recognition domain. CRD).MBL plays an important role in the innate immunity against infection. It uses CRD to selectively recognize and bind to the surface of many pathogens with D-mannose N-acetylglucosamine and N-acetylmannitamine. N-acetylgalactosamine, fucosaccharide, etc. CRD has been found to recognize and bind bacteria, viruses, and yeast. A series of pathogens such as Leishmania spp. MBL activated the complement system by lectin pathway and played the role of bacteriolysis or indirect regulation of phagocytosis. It also binds to the Clq receptor on phagocyte surface and plays a direct role in conditioning. At present, biochemists focus on the molecular mechanism of MBL molecular CRD, while immunologists focus on the microbiological recognition spectrum of CRD. In recent years, studies have shown that CRD can inhibit influenza virus infection in cells, and this effect is not dependent on complement; MBL also interferes with the adhesion of the virus to host cells and affects the transmission and release of the virus. However, the relationship between this effect and the structure of MBL has not been studied. Perhaps just as the Fab fragment of the antibody has neutralizing toxins in addition to recognizing antigens, it acts as well as viruses. The CRD of MBL, especially oligodeoxynucleotidyl (CRD) with high affinity, may have direct effects such as neutralization of virus and inhibition of bacterial adhesion. In order to explore the above possibility, we expressed MBL-CRD gene in Escherichia coli system and obtained the purified recombinant CRD polymer protein. Based on the analysis of ligand binding activity, the direct effect of MBL-CRD on pathogens was studied.
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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