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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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。 随着我们对老年痴呆症和朊病毒疾病的研究取得更大成果，这一点就被忽略了。 因此，在我们的第三年扩展中，我们改变了我们的目标，以探索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β肽的不同同晶型内的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）探测这些蛋白质的突变如何影响铜的配位几何形状，3）检查这些铜-金属蛋白/金属肽支持催化活性氧物质产生的能力，以及4）研究铜、朊病毒蛋白和β淀粉样蛋白之间的相互作用如何影响神经毒性，因为生物化学文献中已经提出了这种联系。