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Structure and complement activating activity of human serum mannan-binding protein

人血清甘露聚糖结合蛋白的结构和补体激活活性

基本信息

批准号：
02454486
负责人：
KAWASAKI Toshisuke
金额：
$ 4.1万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Human serum mannan-binding protein (MBP) is a lectin (carbohydrate binding protein), which was first described by these authors. The lectin has been shown to have the ability to activate complement and also to function as direct opsonin, leading to the concept that the lectin is a novel component associated with selfdefense mechanism. This study was undertaken to examine the structure function relationship particularly on its complement activating activity of the lectin with the results described below.1) Amino acid sequence of the human serum MBP was studied protein chemically. The lectin, which had been reduced and alkylated, was digested with lysylendopeptidase. The resulting peptides were purified by HPLC and then their sequences were determined by a peptide sequencer.2) Human serum MBP cDNA was cloned from human liver cDNA library, which had been carried in lambda gtll, by screening with rat serum MBP cDNA as a probe and the nucleotide sequence of the cloned cDNA was determined by … More dedeoxy termination method. By comparing the result obtained in 1) and 2), human serum MBP was revealed to be composed of 248 amino acids.3) The gross structure of the serum MBP is very similar to a complement component Clq. This prompted to us to study the molecular mechanism of complement activation by the serum MBP. Studies using the other complement components Clr and Cls revealed that the serum MBP, once bound to the solid phase ligands, associates Clr*Cls complement. On this complex, the conversion of Clr*Cls from their zymogen forms to the activated serine proteases proceeds, leading to the activating of a series of cascade reaction of the classical pathway of the complement system.4) The serum MBP was shown to have complement dependent bactericidal activity against E. coli K12, B strains which have haptenic sugars (mannose, NAcetylglucosamine) on their core structure, and also cytotoxic activity against cultured mammalian cells which have high mannose-type oligosaccharide chains on their surfaces. Less

人血清甘露聚糖结合蛋白（MBP）是一种凝集素（碳水化合物结合蛋白），由这些作者首次描述。凝集素已被证明具有激活补体的能力，并且还具有直接调理素的功能，这导致了凝集素是与自卫机制相关的新组分的概念。本研究旨在研究凝集素的结构功能关系，特别是其补体激活活性，结果如下所述。1）对人血清MBP的氨基酸序列进行了蛋白质化学研究。用赖氨酰内肽酶消化已被还原和烷基化的凝集素。2）以大鼠血清MBP cDNA为探针，从λ gt 11载体的人肝cDNA文库中克隆人血清MBP cDNA，并通过测序确定其核苷酸序列。 ...更多信息脱氧终止法通过比较1）和2）中获得的结果，揭示了人血清MBP由248个氨基酸组成。3）血清MBP的总体结构与补体成分Clq非常相似。这促使我们研究血清MBP激活补体的分子机制。使用其它补体成分Clr和Cls的研究揭示，血清MBP一旦与固相配体结合，就与Clr*Cls补体结合。在此复合物上，Clr*Cls从其酶原形式转化为活化的丝氨酸蛋白酶，导致补体系统经典途径的一系列级联反应的活化。coli K12，B菌株，其在其核心结构上具有半抗原糖（甘露糖，N-乙酰葡糖胺），以及对在其表面上具有高甘露糖型寡糖链的培养的哺乳动物细胞的细胞毒性活性。少