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Pathological analysis based molecular interaction of the attachement factors of periodontal pathogens

基于牙周病原菌附着因子分子相互作用的病理学分析

基本信息

批准号：
13671982
负责人：
SHIBATA Yasuko
金额：
$ 1.47万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

The analysis based on the ligand interaction was carried out on erythrocyte aggregating factor (hemagglutinin) and coaggregation factor P. gingivalis mentioned as an attachment factor. First, it should be necessary the Motif/Block search of these molecules of P. gingivalis, thus the specific motif in the hemagglutinin or the coaggregation factor to collate the ligand binding were searched. The primary structure of hemagglutinin of P. gingivalis set against that of influenza virus, and the commonality of activity and structure was compared. It was found that amino acid stretch of functional site of the P. gingivalis hemagglutinin were also exsisting amino acid stretch in influenza virus. We also showed that the human type monoclonal antibodies against the hemagglutinin domain molecules from P. gingivalis inhibited the hemagglutination of influenza virus. Moreover, these antibodies also neutralized the influenza virus infection to cells in vitro. It was proven that there was a cross-reaction of antibodies against the both hemagglutinin molecules of P. gingivalis and influenza virus.Molecular structure elucidation of the coaggregation factor that was related to the oral attachment was tried. The coaggregation factor of P. gingivalis was the multifunctional molecule. We demonstrated this protein was one of the hemin binding proteins. Considering survival of this bacterium and true role of the hemin binding protein, the following were shown : Oxidization reducibility of the hemin molecule and possibility of oxygen inclusion. In addition, it was proven that heme-binding structure of this protein may be based on the cysteine residue. Production of the recombinant proteins that converted the cysteine residues into the serine residues were used to clarify which cysteine residue was related the hemin binding. Interestingly, the active center of the thioredoxin had been made in the two inside, and the relation with the oxidoreduction mechanism was speculated.

对红细胞聚集因子(血凝素)和共聚集因子牙龈假单胞菌进行了基于配体相互作用的分析。首先，必须对牙龈假单胞菌的这些分子进行基序/区块搜索，从而搜索血凝素中的特定基序或共聚集因子来核对配体结合。将牙龈假单胞菌血凝素的一级结构与流感病毒的血凝素一级结构进行比较，并比较其活性和结构的共性。研究发现，在流感病毒中，牙龈假单胞菌血凝素功能部位的氨基酸拉伸也存在。我们还发现，抗牙龈假单胞菌血凝素结构域分子的人型单抗能抑制流感病毒的血凝。此外，这些抗体还在体外中和了流感病毒对细胞的感染。证实了抗牙周血吸虫血凝素分子的抗体与流感病毒存在交叉反应，并试图阐明与口腔附着相关的共聚集因子的分子结构。牙龈假单胞菌的共聚集因子是多功能分子。我们证明该蛋白是一种氯化血红素结合蛋白。考虑到细菌的存活和氯化血红素结合蛋白的真实作用，结果表明：氯化高铁血红素分子的氧化还原能力和氧包涵体的可能性。此外，该蛋白的血红素结合结构可能是以半胱氨酸残基为基础的。将半胱氨酸残基转化为丝氨酸残基的重组蛋白的产生被用来阐明哪些半胱氨酸残基与氯化血红素结合有关。有趣的是，硫氧还蛋白的活性中心位于其中的两个位置，并推测了其与氧化还原机理的关系。