PROBING THE INFLUENCE OF ARGININE METHYLATION ON THE MODULATION OF BIOMOLECULAR

探讨精氨酸甲基化对生物分子调节的影响

• 批准号: 8360611
• 负责人: Jason M Shearer
• 金额: $ 7.67万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360611
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Arginine; Biochemical; Biomedical Research; Copper; Funding; Goals; Grant; Investigation; Link; Literature; Metalloproteins; Metals; Methylation; Mutation; National Center for Research Resources; Principal Investigator; Prion Diseases; Prions; Production; Proteins; Reactive Oxygen Species; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; cost; neurotoxic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our original goals were to investigate the influence of arginine methylation on biomolecular interactions. This took a sideline as our investigations into Alzheimer's and prion disease were more fruitful. Therefore in our year three extension we altered our goals to probe the neurotoxic consequences of copper coordination to the prion protein and amyloid-beta peptides. Our goals are to: 1) determine the Cu(I) and Cu(II) coordination geometries within different isomorphs of the prion protein and amyloid-beta peptide as coordination geometry directly influence metal center reactivity, 2) probe how mutations to these proteins influence the coordination geometry of copper, 3) examine the ability of these copper-metalloproteins/metallopeptides to support catalytic reactive oxygen species production and 4) examine how the interaction between the copper, the prion-protein and amyloid-beta influence neurotxicity as such a link has been suggested in the biochemical literature.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们最初的目标是研究精氨酸甲基化对生物分子相互作用的影响。 随着我们对阿尔茨海默氏症和朊病毒病的研究更加富有成果，这一点就被搁置了。 因此，在第三年的扩展中，我们改变了目标，以探究铜与朊病毒蛋白和淀粉样β肽配位的神经毒性后果。 我们的目标是：1) 确定朊病毒蛋白和淀粉样蛋白-β 肽的不同同种型内的 Cu(I) 和 Cu(II) 配位几何形状，因为配位几何形状直接影响金属中心反应性，2) 探究这些蛋白质的突变如何影响铜的配位几何结构，3) 检查这些铜金属蛋白/金属肽支持催化活性氧生成的能力，4) 检查铜、朊病毒蛋白和淀粉样蛋白-β影响神经毒性，生化文献中已经提出了这种联系。