SMALL ANGLE X-RAY SCATTERING STUDIES OF THE DISAGGREGASE HSP104

解聚酶 HSP104 的小角 X 射线散射研究

• 批准号: 8361280
• 负责人: KUSHOL GUPTA
• 金额: $ 0.59万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361280
• 关键词: Agreement; Biophysics; Centromere; Chromosomes; Complex; DNA Sequence; Epigenetic Process; Funding; Grant; Histones; Location; National Center for Research Resources; Nature; Principal Investigator; Proteins; Publishing; Research; Research Infrastructure; Resolution; Resources; Roentgen Rays; Solutions; Source; Specific qualifier value; Structure; To specify; United States National Institutes of Health; Variant; Work; base; centromere protein A; cost; research study

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. We sought to compare the low resolution solution structures of conventional histone complexes and their counterpart at the centromere, the region of the chromosome that directs its own inheritance. Our hypothesis going into these studies was that structural alteration in the centromeric histone 'variant', CENP-A, are important for epigenetically marking the centromere locus. Previous findings had indicated that the location of mammalian centromeres is not specified by a particular DNA sequence and there is strong evidence that there is a strong epigenetic component to specifying centromere location. Our SAXS experiments are key to our efforts to define the physical basis for the epigenetic centromere 'mark'. We found that the centromere version of the complex is more compact than the conventional complex by ~10 angstroms. This was in general agreement with our findings from crystal structures of the same proteins. This work was a critical component of the study that was just published in Nature.

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。 我们试图比较传统组蛋白复合物的低分辨率解决方案结构及其在着丝粒（指导其自身遗传的染色体区域）的对应物。我们对这些研究的假设是，着丝粒组蛋白“变体”CENP-A 的结构改变对于表观遗传学标记着丝粒位点很重要。先前的研究结果表明，哺乳动物着丝粒的位置并不是由特定的 DNA 序列指定的，并且有强有力的证据表明，存在着强烈的表观遗传成分来指定着丝粒的位置。我们的 SAXS 实验是我们努力定义表观遗传着丝粒“标记”物理基础的关键。 我们发现着丝粒版本的复合体比传统复合体紧凑约 10 埃。这与我们从相同蛋白质的晶体结构中得到的发现大体一致。这项工作是刚刚发表在《自然》杂志上的研究的重要组成部分。