Structural and biophysical studies of proteins, nucleic acids, and their complexes

蛋白质、核酸及其复合物的结构和生物物理研究

• 批准号: 10001067
• 负责人: Alfonso Mondragon
• 金额: $ 54.92万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001067
• 关键词: Antibiotics; Archaea; Architecture; Bacteria; Biochemical; Biological; Biological Process; Catalysis; Catalytic RNA; Cell physiology; Cells; Complex; DNA; Ensure; Eukaryota; Evolution; Goals; Human; Life; Malignant Neoplasms; Nucleic Acids; Organism; Property; Proteins; RNA; RNA Processing; RNase P; Research; Research Design; Ribonucleases; Ribonucleoproteins; Role; Structure; Therapeutic Agents; Topoisomerase; Topoisomerase II; Work; biophysical analysis; chemotherapeutic agent; design; macromolecule; novel therapeutics; public health relevance; single molecule

 DESCRIPTION (provided by applicant): The central theme of this proposal is structural and mechanistic studies of nucleic acids, proteins, and their interactions. The two broad topics that will serve as foci for our research are: 1) the structure and mechanism of topoisomerases, and 2) the structure, architecture, and mechanism of RNase P. The aim of our work is to discover and explore paradigms that help to illuminate the structure and mechanism of biological molecules common to all three domains of life (bacteria, archaea, and eukaryota). Topoisomerases are ubiquitous proteins found across all three domains of life. They are involved in several cellular processes and the importance of their cellular role is underscored by the fact that they are the target of several cancer chemotherapeutic agents and antibiotics. The study of the structure, mechanism, and function of topoisomerases not only furthers our understanding at many different levels of proteins that interact with DNA and alter its topological properties, but also provides important information to aid in the design of new therapeutic agents. To accomplish our goals, our comprehensive studies of topoisomerases will focus on two large and complementary projects: Project 1. Structural and biochemical studies of type IA, type IC and type II topoisomerases, and Project 2. Single molecule studies of type IA and type II topoisomerases. These two major projects will help answer crucial questions that are needed to advance the field to the next level. RNase P is a ribonucleoprotein complex found in almost all organisms, from bacteria to humans, and responsible for processing many different RNA molecules in the cell. It is composed of one essential RNA subunit and one or more proteins, but in all cases the RNA component is responsible for catalysis. RNase P was one of the first catalytic RNA molecules discovered and its study has been pivotal to our understanding of the role of RNA molecules in catalysis. Our studies of the structure and function of RNase P are providing important and relevant information on a key ribozyme involved in RNA processing in the cell, while also furthering our understanding of the structure and function of large RNA molecules and ribonucleoprotein complexes. To ensure that RNase P continues to be a paradigm for understanding RNA structure and function, large ribonucleoprotein complexes, and also the evolution from the ancient RNA world, a third project, Project 3. Structural and biophysical studies of RNase P, will be centered on structural and functional studies on RNase P expanding it to include RNase Ps from all three domains of life.

 描述（由申请人提供）：该提案的中心主题是核酸、蛋白质及其相互作用的结构和机制研究，这两个广泛的主题将成为我们研究的重点：1）拓扑异构酶的结构和机制。 ，和 2) RNase P 的结构、架构和机制。我们工作的目的是发现和探索有助于阐明生命所有三个领域（细菌、拓扑异构酶是在生命的所有三个领域中普遍存在的蛋白质，它们参与多种细胞过程，并且它们是多种癌症化疗药物和抗生素的靶标，这一事实强调了它们的细胞作用的重要性。对拓扑异构酶的结构、机制和功能的研究不仅进一步加深了我们对与 DNA 相互作用并改变其拓扑结构的蛋白质的许多不同水平的理解。 性质，而且还提供重要信息来帮助设计新的治疗剂 为了实现我们的目标，我们对拓扑异构酶的全面研究将集中于两个大型且互补的项目：项目 1. IA 型、IC 型和 IA 型的结构和生化研究。 II 型拓扑异构酶和项目 2。IA 型和 II 型拓扑异构酶的单分子研究这两个主要项目将有助于回答将 RNase P 领域提升到新水平所需的关键问题。核糖核蛋白复合物存在于从细菌到人类的几乎所有生物体中，负责在细胞中加工许多不同的 RNA 分子。它由一个必需的 RNA 亚基和一种或多种蛋白质组成，但在所有情况下，RNA 成分都负责催化。 RNase P 是最早发现的催化 RNA 分子之一，它的研究对于我们理解 RNA 分子在催化中的作用至关重要。我们对 RNase P 结构和功能的研究为关键提供了重要且相关的信息。核酶参与细胞中的 RNA 加工，同时也进一步加深了我们对大 RNA 分子和核糖核蛋白复合物的结构和功能的理解，以确保 RNase P 继续成为理解 RNA 结构和功能、大核糖核蛋白复合物的范例。古代RNA世界的进化，第三个项目，项目3。RNase P的结构和生物物理研究，将集中于RNase P的结构和功能研究，将其扩展到包括RNase来自生活所有三个领域的 Ps。