Analyses of prion structure using deletion mutants of prion protein

使用朊病毒蛋白缺失突变体分析朊病毒结构

• 批准号: 11680731
• 负责人: MURAMOTO Tamaki
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680731/
• 关键词: prion; conformation; mutation; bioassay; gene therapy; amyloid; neuronal degeneration; transgenic mice

Prions, the causative agents of prion diseases, are mainly composed of the infectious form of prion protein (PrPSc). The main event of prion proliferation is the conformational change of the cellular form of prion protein (PrPC), a normal component of neurons, into the infectious form through PrPC-PrPSc interaction. The mechanism of this isoform conversion of prion protein (PrP) remains enigmatic.In order to solve this issue, we determined the domains of PrP that are essential for the isoform conversion. In addition, we discovered unique phenomena caused by deletion mutants of PrP. Some mutant PrPs with one of the essential domains deleted inhibited the isoform conversion of wild type PrP while the other deletion mutant markedly enhanced PrP amyloid deposition when mice co-expressing the wild type and mutant PrPs are inoculated with prions. These data not only provide insights about the mechanism of prion and amyloid formation by PrP but also initiate new studies toward the development of methods to treat or prevent prion diseases using mutant PrPs.

prions是病毒疾病的病因，主要由感染形式的prion蛋白（PRPSC）组成。 Prion增殖的主要事件是通过PRPC-PRPSC相互作用进入传染性形式的Prion蛋白（PRPC）的细胞形式（PRPC）的构象变化。 Prion蛋白（PRP）的同工型转化的机制仍然神秘。为了解决此问题，我们确定了对于同工型转换至关重要的PRP域。此外，我们发现了由PRP的缺失突变体引起的独特现象。一些具有必需结构域之一的突变体PRP抑制了野生型PRP的同工型转化，而另一个缺失突变体显着增强了PRP淀粉样蛋白的沉积，当共表达野生型PRP的小鼠与prions接种。这些数据不仅提供了有关PRP的prion和淀粉样蛋白形成机制的见解，而且还为使用突变PRP的方法启动了新的研究，以开发方法来治疗或预防病毒疾病。

项目成果

Identification of two prion protein regions that modify scrapie incubation time.

鉴定两个改变瘙痒病孵育时间的朊病毒蛋白区域。

• 发表时间: 2001
• 期刊: Journal of Virology 75(3)
• 作者: Supattapone S;Muramoto T;Legname G;et al.
• 通讯作者: et al.

Analyses of Gerstmann-Straussler syndrome with 102Leu219Lys using monoclonal antibodies that specifically deted human prion protein with 219Glu.

使用单克隆抗体对 102Leu219Lys 进行的 Gerstmann-Straussler 综合征进行分析，该抗体专门检测带有 219Glu 的人朊病毒蛋白。

• 发表时间: 2000
• 期刊: Neuroscience Letters 288(3)
• 作者: Muramoto T;Tanaka T;Kitamoto N;et al.
• 通讯作者: et al.