Chaperone-amyloid interactions

伴侣-淀粉样蛋白相互作用

• 批准号: 7967200
• 负责人: Daniel Masison
• 金额: $ 9.94万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7967200
• 关键词: Affect; Amyloid; Biochemical; Genetic; Goals; In Vitro; Kinetics; Mediating; Methods; Molecular; Molecular Chaperones; Mutation; Phenotype; Prions; Property; Proteins; Structure; Work; amyloid formation; falls; in vivo; mutant

We have been focusing our approach on studying how alterations in primary structure of prion proteins can affect chaperone interactions. We have been isolating mutants of prion proteins that fall into two major classes, those that interfere with propagation of prions formed of wild type proteins and those that don't. Both types of mutants contain subclasses that, in the absence of wild type protein, either form prions with weakened phenotypes or are unable to form prions. We are using genetic and biochemical methods to determine if the observed effects on prion phenotpye are due to differences in how the prion proteins self-associate or interact with various chaperones. Our preliminary work suggests that the prion protein mutations can influence propagation of amyloid or the interaction of chaperones that in turn affect how efficiently the prions propagate.

我们一直将我们的方法集中在研究王室蛋白主要结构的变化如何影响伴侣相互作用的方式上。我们一直在隔离落入两个主要类别的prion蛋白的突变体，这些类别会干扰由野生型蛋白质和不繁殖的prions的传播。两种类型的突变体都包含子类，在没有野生型蛋白质的情况下，要么形成弱的表型prions，要么无法形成王室。 我们使用遗传和生化方法来确定观察到的对prion菌的影响是由于prion蛋白如何自我缔合或与各种伴侣相互作用的差异。我们的初步工作表明，prion蛋白突变会影响淀粉样蛋白的传播或伴侣的相互作用，而伴侣的相互作用反过来影响王室的传播效率。