Structure of the Eukaryote Transcription Apparatus

真核生物转录装置的结构

• 批准号: 7633902
• 负责人: ROGER D KORNBERG
• 金额: $ 21.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7633902
• 关键词: 3-Dimensional; California; Chromatin Remodeling Factor; Cities; Complement Factor B; Complement Factor H; Complex; Cryoelectron Microscopy; Eukaryota; Eukaryotic Cell; Face; Fourier Analysis; General Transcription Factors; Genetic Transcription; Goals; Growth; Human Resources; Ice; Inherited; Instruction; Lipids; Mediator of activation protein; Molecular; Mutation; Names; Negative Staining; Nucleosomes; Numbers; Postdoctoral Fellow; Principal Investigator; Printing; Proteins; Prothrombin; RNA Polymerase II; Regulation; Research Personnel; Research Project Grants; Resolution; Roentgen Rays; Role; Site; Specimen; Structure; Syndrome; Testing; Transcription Initiation; Transcriptional Activation; Universities; Work; base; dalton; electron crystallography; human disease; image processing; interest; medical schools; particle; programs; size; transcription factor; tumorigenesis

The goal of our work is the structural elucidation of the large multiprotein assemblies involved in RNA polymerase II transcription. We have isolated and performed preliminary structural studies on a chromatin- remodeling complex (RSC), general transcription factors, and Mediator. Specific aims for the project period are structure determination of (1) general transcription factor H, (2) RNA polymerase II - general transcription factor complexes, (3) Mediator and Mediator - RNA polymerase II complexes, and (4) RSC and RSC - nucleosome complexes. Our efforts will culminate in the structure determination of a complete 48-protein RNA polymerase II transcription initiation complex, and of a RSC-nucleosome complex in the transcriptionally activated state. In view of the size of these complexes, almost all greater than one million Daltons, structures will be determined by cryoelectron microscopy and image processing. Wherever possible, 2-D crystals will be formed on lipid layers, permitting image processing by Fourier analysis. In the absence of crystals, image processing will be done by single particle analysis. The results should reveal the molecular basis of transcriptional activation, initiation,and regulation. They will be directly relevant to human disease. For example, mutations in subunits of factor H are responsible for a number of inherited human disease syndromes. Mutations in RSC or RSC-related proteins are implicated in oncogenesis. =>ERFORMANCE SITE(S) (organization, city, state) Stanford University School of Medicine Stanford, California 94305-5126 KEY PERSONNEL. See instructions on Page 11. Usecontinuationpagesas neededto provide the required information in the format shown below. Name Organization Role on Project ROGER D. KORNBERG STANFORD UNIVERSITY P.I. DAVID A. BUSHNELL STANFORD UNIVERSITY POSTDOC FELLOW PHS 398 (Rev. 4/98) Page2 BB Number pages consecutively at the bottom throughout the application. Do ngiuse suffixes such as 3a, 3b. CC ^ropal Investigator/Program Director (Last, first, middle^* Kornberg. Roger D. Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page Description,

我们工作的目标是阐明RNA中涉及的大型多蛋白组装体的结构 聚合酶II转录。我们已经分离并初步研究了一种染色质- 重塑复合物（RSC）、一般转录因子和介体。项目期间的具体目标是 （1）通用转录因子H，（2）RNA聚合酶II -通用转录因子结构测定 复合物，（3）介体和介体- RNA聚合酶II复合物，以及（4）RSC和RSC -核小体 配合物我们的努力将最终确定一个完整的48蛋白RNA聚合酶的结构 II转录起始复合物，以及转录激活状态的RSC-核小体复合物。在 考虑到这些复合物的大小，几乎所有都大于一百万道尔顿，结构将由下式确定： 冷冻电子显微镜和图像处理。只要有可能，2-D晶体将在脂质层上形成， 允许通过傅立叶分析进行图像处理。在没有晶体的情况下，图像处理将通过 单粒子分析这些结果将揭示转录激活、起始和转录调控的分子基础。 调控它们将与人类疾病直接相关。例如，因子H亚基的突变是 导致许多遗传性人类疾病综合征。RSC或RSC相关蛋白的突变是 与肿瘤发生有关 =>业绩地点（组织、城市、州） 斯坦福大学 医学院 斯坦福大学，加州94305-5126 关键人员。参见第11页的说明。需要使用续页以下列格式提供所需信息。 名称组织在项目中的角色 罗杰·D康恩伯格斯坦福大学体育学院 大卫A.布什内尔斯坦福大学博士后研究员 PHS 398（Rev. 4/98）第2页BB 在整个应用程序的底部连续编号页面。不要使用后缀，如3a，3b。 CC ^ropal研究员/项目总监（最后，第一，中间^* Kornberg。罗杰·D 在各打印页和各续页的顶部键入主要研究者/项目负责人的姓名。(For型号规格，见 第6页的说明）。 研究资助 目录 页码 首页 产品描述：