STRUCTURAL BIOLOGY OF BACTERIAL PATHOGENS

细菌病原体的结构生物学

• 批准号: 7954395
• 负责人: marek Jedrzejas
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954395
• 关键词: Acids; Bacillus (bacterium); Biochemical; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; DNA; DNA biosynthesis; DNA-Binding Proteins; Funding; Germination; Goals; Grant; Institution; Lead; Molecular; Peptide Hydrolases; Polymerase; Property; Proteins; Reproduction spores; Research; Research Personnel; Resources; Source; United States National Institutes of Health; novel; pathogen; protein complex; protein degradation; structural biology; success; synchrotron radiation; three dimensional structure

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. The objectives of the research are to investigate 1) the mechanisms whereby a group of novel DNA-binding proteins, termed alpha/beta-type small, acid-soluble proteins (SASP) protect DNA in dormant spores of Bacillus species against a variety of damaging agents, and 2) how these proteins are subsequently removed during spore outgrowth, ultimately leading to 3) chromosomal replication. The studies will involve biochemical and biophysical elucidation of the properties of the alpha/beta-type SASP and the complexes of these proteins with DNA, the characterization of the spore protease, termed Gpr, that initiates SASP degradation during spore outgrowth, as well as characterization of PolE and PolC (apo and complexes with DNA template:primers) novel bacterial polymerases responsible for chromosomal DNA replication. A major goal of the proposed research is the characterization (mechanistic and functional) of all of these components including elucidation of their three-dimensional structures by x-ray crystallography. Success in achieving this goal will lead to an understanding at the molecular level of the mechanisms of DNA protection in dormant spores, the mechanisms responsible for the loss of this DNA protection during spore germination and outgrowth, and later mechanism of its replication in vegetative cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该研究的目的是调查 1) 一组新型 DNA 结合蛋白（称为 α/β 型小酸溶蛋白 (SASP)）保护芽孢杆菌属休眠孢子中的 DNA 免受各种破坏剂侵害的机制，以及 2) 这些蛋白质随后如何在孢子生长过程中被去除，最终导致 3) 染色体复制。这些研究将涉及对 α/β 型 SASP 的特性以及这些蛋白质与 DNA 的复合物的生化和生物物理阐明，孢子蛋白酶（称为 Gpr）的表征（它在孢子生长过程中启动 SASP 降解），以及 PolE 和 PolC（apo 和与 DNA 模板的复合物：引物）的表征，这些新型细菌聚合酶负责 染色体DNA复制。拟议研究的一个主要目标是表征所有这些组件（机械和功能），包括通过 X 射线晶体学阐明其三维结构。成功实现这一目标将有助于在分子水平上了解休眠孢子中 DNA 保护的机制、孢子萌发和生长过程中 DNA 保护丧失的机制，以及随后在营养细胞中复制的机制。