STRUCTURE DETERMINATION OF THE CHD1 DNA-BINDING DOMAIN

CHD1 DNA 结合域的结构测定

• 批准号: 8363383
• 负责人: GREGORY DEAN BOWMAN
• 金额: $ 0.31万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363383
• 关键词: Binding; Complex; Coupled; Crystallography; DNA; DNA Binding; DNA Binding Domain; Funding; Genetic Transcription; Grant; L-Selenomethionine; Light; National Center for Research Resources; Nucleosome Core Particle; Nucleosomes; Phase; Principal Investigator; Relative (related person); Research; Research Infrastructure; Resolution; Resources; Slide; Source; Structure; Synchrotrons; United States National Institutes of Health; Yeasts; chromatin remodeling; cost

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. Chd1 is a chromatin remodeler that participates in gene transcription by manipulating nucleosome structure. By sliding nucleosomes along DNA, Chd1 is known to generate evenly-spaced nucleosomal arrays, and we have found that the Chd1 DNA-binding domain is essential for sensing the relative distances between nucleosomes. The Chd1 DNA-binding domain binds DNA in a sequence-nonspecific fashion, and current questions include (1) how the DNA-binding domain interacts with DNA just outside the nucleosome core, (2) whether binding is coupled to conformational changes in the DNA duplex, and (3) whether DNA binding by Chd1 would be expected to be compatible with DNA associating with the nucleosome (i.e. promote release of the DNA-binding domain). We currently have crystals of the yeast Chd1 DNA-binding domain in complex with a 12mer DNA duplex that diffract to better than 2.3 angstrom resolution. We have grown small SeMet crystals and hope to obtain phases and solve the structure.

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。 Chd1 是一种染色质重塑因子，通过操纵核小体结构参与基因转录。通过沿着 DNA 滑动核小体，Chd1 可以生成均匀间隔的核小体阵列，并且我们发现 Chd1 DNA 结合域对于感测核小体之间的相对距离至关重要。 Chd1 DNA 结合结构域以序列非特异性方式结合 DNA，当前的问题包括 (1) DNA 结合结构域如何与核小体核心外部的 DNA 相互作用，(2) 结合是否与 DNA 双链体中的构象变化偶联，以及 (3) Chd1 的 DNA 结合是否预期与与核小体结合的 DNA 相容（即促进 DNA 结合域的释放）。我们目前拥有与 12mer DNA 双链体复合的酵母 Chd1 DNA 结合结构域晶体，其衍射分辨率优于 2.3 埃。我们已经生长了小型 SeMet 晶体，希望获得相并解析其结构。