GENETIC STUDY OF THE YEAST PRION INTERACTING PROTEINS

遗传性神经退行性脑病(称为普恩 哺乳动物和人类的疾病)，以及与年龄有关的病理 如阿尔茨海默氏症，与有核聚合有关。 形成蛋白质聚集体的过程。普恩病毒病 阿尔茨海默氏症是致命的，是无法治愈的。“纯蛋白质” Prion病的模型表明，异常的Prion蛋白可能 作为一种感染剂，通过“播种”形成新的普恩病毒。 酵母菌中发现的类Pron蛋白 Cerevisiae意味着广泛的分布和可能的生物学 普里子现象的重要性。从遗传学家S的观点来看， 普恩现象的“纯蛋白质”模型表明，此外 与由序列编码的信息、某些蛋白质和/或 多蛋白质结构包含“编码”的额外信息。 在结构本身。高度有序的细胞结构，如 细胞骨架结构，是最有可能的系统候选者 “结构化”编码。 拟议的项目旨在检验一种假设，该假设表明 Prion聚集体的出现是由于一种流产的形式 结构形成过程，通常导致有序的组装 胞内或胞外多蛋白复合体。酵母蛋白- 形成平移释放因子Sup35p(ERF3)将用作 实验模型。伴侣助手和细胞骨架的作用- 与Sup35pPSI蛋白的形成和繁殖相关的蛋白质， 在细胞骨架组装中将通过使用基因和 生化方法。蛋白质之间的相互作用，这涉及到 将对Sup35p的Prion形成结构域进行表征。结果 所获得的结果将阐明这些机制，整合潜在的 Pron形成过程进入正常细胞生理过程，并可能 最终导致了Pron疾病的新疗法的开发和 相关的障碍。

The transmissible neurodegenerative encephalopathies (called prion diseases) in mammals and humans, as well as age-related pathologies such as Alzheimer's syndrome, are associated with a nucleated polymerization" process leading to the formation of protein aggregates. Prion diseases and Alzheimer's syndrome are fatal and incurable. The "protein only" model of prion diseases suggests that abnormal prion protein may serve as an infectious agent by "seeding" formation of the new prions. Recent finding of prion-like proteins in the yeast Saccharomyces cerevisiae suggests a wide distribution and possible biological importance of prion phenomena. From the geneticist' s point of view, the "protein only" model of prion phenomena suggests that, in addition to the information which is coded by the sequence, some protein and/or multiprotein structures contain additional information which is "coded" in the structure itself. Highly ordered cellular structures such as cytoskeletal formations, are the most likely candidates for the systems of "structural" coding. The proposed project is designed to test a hypothesis, which states that the appearance of prion aggregates results from an abortive form of the structure-forming process, normally leading to assembly of the ordered intracellular or extracellular multiprotein complexes. The yeast prion- forming translational release factor Sup35p (eRF3) will be used as an experimental model. Roles of the chaperone helpers and cytoskeleton- associated proteins in formation and propagation of the Sup35pPSI prion, and in the cytoskeletal assembly will be compared by using genetic and biochemical approaches. Protein-protein interactions, which involve the prion-forming domain of the Sup35p, will be characterized. Results obtained will shed light on the mechanisms, integrating the potential prion-forming processes into normal cellular physiology, and may eventually lead to the development of new cures for prion diseases and related disorders.