MOLECULAR MECHANISM OF HISTONE ACETYLATION

组蛋白乙酰化的分子机制

基本信息

批准号：
8170603
负责人：
Yu Yuan
金额：
$ 1.39万
依托单位：
BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2011-06-30
项目状态：
已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eukaryotic DNA is packed in nucleosomal particles for assembly into high-order structures in the nucleus. Histone modifications in patterns mediated by numerous protein complexes are important for almost all DNA-related processes. Chromatin remodelling complexes can be grouped into two categories depending on nucleosomal conformational alteration or chromatin conformational alteration.Histone acetylation is responsible for chromatin conformational alteration, while Histone acetyltransferases (HATs) are the catalytic subunits of large multiprotein complexes that acetylate the N-terminal tail regions of histones to facilitate transcription activation in eukaryotes.Structural bases for histone modifications mediated by protein-protein complexes are critical to understand these processes. Although during past one decade, significant structural progresses are obtained to understand histone posttranslational modifications including acetylation, phosphorylation, methylation and ubiquitination [reviewed in 4], there are still a lot of unanswered questions: such as how many hotspots exist for modification within histone tails, how many different structural modules can recognize one single histone modification, how many different histone modification sites a single structural module can recognize, how many structural modules can be combined to recognize one single histone modification. In the long term, I would like to answer all these fundamental questions from the structural and molecular view by targeting several critical histone supercomplexes. At this proposal, I outline below a combination of structural and biochemical approaches to study protein-peptide recognition and protein-protein interaction events associated with Histone Code, such as Rtt109 complex mediated H3K56 acetylation and NuA4 complex mediated H4K16 acetylation

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。真核DNA堆积在核小体颗粒中，以使组装成核中的高阶结构。许多蛋白质复合物介导的模式中的组蛋白修饰对于几乎所有与DNA相关的过程都很重要。 Chromatin remodelling complexes can be grouped into two categories depending on nucleosomal conformational alteration or chromatin conformational alteration.Histone acetylation is responsible for chromatin conformational alteration, while Histone acetyltransferases (HATs) are the catalytic subunits of large multiprotein complexes that acetylate the N-terminal tail regions of histones to facilitate transcription activation in真核生物。由蛋白质蛋白质复合物介导的组蛋白修饰的结构基础对于了解这些过程至关重要。尽管在过去的十年中，获得了重大的结构进步，以理解翻译后修饰，包括乙酰化，磷酸化，甲基化和泛素化[4]综述[4]综述，仍然存在许多未解决的问题：例如，存在许多较大的模块化模构，有很多模块化的模块化，许多热点可以识别出多种构造的模块，有多少个模块化，许多构造的位置，有多少个模块化的模块化，有多少个模块化的模块，这些模构元素可以不同。认识到，可以组合多少个结构模块以识别一种单一的组蛋白修饰。从长远来看，我想通过靶向几个关键的组蛋白超复合物来回答从结构和分子视图中回答所有这些基本问题。在该提案中，我概述了研究蛋白质肽识别和与组蛋白代码相关的蛋白质肽识别和蛋白质 - 蛋白质相互作用事件（例如RTT109复合物介导的H3K56乙酰化和NUA4复合物介导的H4K16乙酰化）的结构和生化方法的组合