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Studies on the physiological function of sugar chains and the activation mechanism of human von Willebrand factor

糖链生理功能及人血管性血友病因子激活机制研究

基本信息

批准号：
09671139
负责人：
MATSUI Taei
金额：
$ 1.86万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671139/
关键词：
von Willebrand factor blood group antigen bone marrow transplantation platelet snake venom protease amino acid sequence lectin ABO血液型 cDNA メタロプロテアーゼビチセチン一次構造 ELISA セリンプロテアーゼブラジキニン

项目摘要

1. The complete amino acid sequence of bitiscetin, a novel von. Willebrand factor (vWF) modulator protein from Bitis arietans snake venom, was determined. Bitiscetin was composed of disulfidelinked heterodimer of alpha and beta subunits. Both the subunits showed a C-type lectin motif and only 45% similarity to another modulator, botrocetin. The competition study suggests that bitiscetin binds to a site in the A1 domain of vWF located closely to the botrocetin-binding site.2. ABO blood group antigen expression on plasma vWF of the patients who received ABO-mismatched bone marrow transplantation was monitored. Blood group antigens on the red blood cells gradually turned to the donor's type, but the antigens on the vWF still maintained the original recipient's type even after several years. The same results were obtained in the case of ABO-mismatched peripheral blood and cord blood stem cell transplantation.3. A novel vWF-binding and -cleaving metalloproteinase named kaouthiagin was purified from Naja kaouthia cobra venom. Kaouthiagin specifically cleaved vWF between Pro-708 and Asp-709 to diminish the multimeric structure of vWF, resulting in the loss of ristocetin-induced platelet aggregability and collagen-binding activity of vWF.4. A novel platelet GPIb-binding protein named mamushigin was purified from A.blomhoffii snake venom and the cDNA of mamushigin was cloned.5. A novel fibrinogen-cleaving serine protease named halystase was purified from the snake venom of Agkistrodon halys blomhoffii and the complete amino acid sequence of halystase was determined. Halystase also cleaved plasma kininogen to produce bradykinin, causing the hypotension in rat.

1.一种新的von.本文报道了一种从Bitisarietans蛇毒中提取的血管性血友病因子（vWF）调节蛋白。双硫键由α和β亚基的二硫键连接的异源二聚体组成。这两个亚基显示C型凝集素基序和只有45%的相似性，另一个调制器，botrocetin。竞争性研究表明，bitisclavin结合到vWF的A1结构域中的一个位点，该位点靠近botrocetin结合位点。监测ABO血型不合骨髓移植患者血浆vWF上ABO血型抗原的表达。红细胞上的血型抗原逐渐转向供体的血型，但vWF上的抗原即使在几年后仍然保持原始受体的血型。ABO血型不合的外周血和脐带血造血干细胞移植也获得了同样的结果.从眼镜蛇毒中分离纯化了一种新的能结合和切割vWF的金属蛋白酶，命名为Kaouthiagin。Kaouthiagin特异性切割Pro-708和Asp-709之间的vWF，以减少vWF的多聚体结构，导致ristocetin诱导的血小板聚集性和vWF的胶原结合活性丧失。从布氏不动杆菌蛇毒中分离纯化了一种新的血小板GPIb结合蛋白，命名为mamushigin，并克隆了mamushigin的cDNA.从浙江产蝮蛇蛇毒中分离纯化了一种新的纤维蛋白原丝氨酸蛋白酶，命名为halystase，并测定了其氨基酸序列。溶血酶还能裂解血浆激肽原产生缓激肽，引起大鼠低血压。