STRUCTURAL BIOLOGY OF BACTERIAL PATHOGENS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 该研究的目的是调查1）一组新的DNA结合蛋白，称为α/β型小酸溶性蛋白（SASP）保护芽孢杆菌物种休眠孢子中的DNA免受各种破坏剂的机制，以及2）这些蛋白质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α/β型SASP和这些蛋白质与DNA的复合物的性质的生物化学和生物物理学阐明，孢子蛋白酶的表征，称为Gpr，在孢子生长过程中启动SASP降解，以及PolE和PolC（载脂蛋白和DNA模板复合物：引物）负责染色体DNA复制的新型细菌聚合酶的表征。拟议研究的一个主要目标是所有这些组件的表征（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导致在分子水平上理解休眠孢子中DNA保护的机制，孢子萌发和生长过程中DNA保护丧失的机制，以及后来在营养细胞中复制的机制。

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.