CHARACTERIZATION OF HUMAN HISTONES WITH COMPLEX PTMS BY ECD

通过 ECD 对具有复杂 PTMS 的人类组蛋白进行表征

• 批准号: 8363779
• 负责人: ALMA L BURLINGAME
• 金额: $ 3.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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/8363779
• 关键词: Acetylation; Cells; Complex; Cues; Epigenetic Process; Funding; Grant; Histones; Human; Location; Mass Spectrum Analysis; Methylation; Modification; National Center for Research Resources; Nature; Phosphorylation; Population; Principal Investigator; Proteins; Proteomics; Regulation; Research; Research Infrastructure; Resources; SHFM1 gene; Site; Source; Ubiquitination; United States National Institutes of Health; Ursidae Family; base; combinatorial; cost; new technology; response

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. Although core histones are among the most conserved proteins in the cell, they bear an extensive population of methylations, acetylations, phosphorylations, and ubiquitination as well as particular additional key modifications throughout their sequences. The various combinations of different numbers of PTMs at different residue locations allow the cell to generate many different PTM configurations as well as alter particular sites dynamically in response to cellular cues. It has been proposed that those configurations are associated with epigenetic regulations. However, detailed characterization of core histones and their PTM configurations is thus far a difficult task. The difficulty for analysis of heavily modified histones arises from the fact that many, sometimes thousands of possible PTM configurations may exist due to the combinatorial nature of PTMs, occupying different sites. In this project, we intend to develop novel technologies to solve some of the most challenging problems in the mass spectrometry based proteomics filed.

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。 尽管核心组蛋白是细胞中最保守的蛋白质之一，但它们在整个序列中具有大量的甲基化、乙酰化、磷酸化和泛素化以及特定的额外关键修饰。不同残基位置上不同数量的 PTM 的各种组合允许细胞生成许多不同的 PTM 配置，并根据细胞提示动态改变特定位点。有人提出这些配置与表观遗传调控有关。然而，核心组蛋白及其 PTM 配置的详细表征迄今为止是一项艰巨的任务。分析严重修饰的组蛋白的困难在于，由于 PTM 的组合性质，占据不同位点，因此可能存在许多、有时数千种可能的 PTM 配置。 在这个项目中，我们打算开发新技术来解决基于质谱的蛋白质组学领域中一些最具挑战性的问题。