Structural Characterizations of Transient and Heterogeneous Protein Complexes

瞬时和异质蛋白质复合物的结构表征

基本信息

批准号：
8895472
负责人：
Nozomi Ando
金额：
$ 24.9万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-02 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895472
关键词：
Allosteric Regulation Amino Acids Antineoplastic Agents Arakawa syndrome 2 Behavior Biochemical Biological Process Biology Cell Cycle Cells Chemicals Complement Complex Congenital Abnormality Crystallization Crystallography DNA biosynthesis Data Deoxyribonucleotides Disease Drug Design Drug Targeting Effectiveness Enzymes Escherichia coli Funding Gene Mutation Goals Heart Human Individual Investigation Kinetics Learning Link Malignant Neoplasms Megaloblastic Anemia Mentors Metabolism Methionine Methods Modeling Molecular Biology Molecular Conformation Nature Neural tube Nucleotides Organism Pharmaceutical Preparations Phase Physiological Play Pregnancy Protein Isoforms Proteins Public Health Regulation Research Ribonucleotide Reductase Roentgen Rays Role S-Adenosylmethionine Sampling Solutions Spectrum Analysis Structure System Time Training Vitamin B 12 Work analytical ultracentrifugation base flexibility in vivo insight mathematical methods meetings prevent protein complex

项目摘要

Transient and heterogeneous protein interactions play important roles both in the catalytic and regulatory functions of protein complexes and multi-modular machinery. However, the technical challenges involved in structural characterizations of such systems have placed critical barriers against understanding their intrinsic behavior. The vitamin B12-dependent methionine synthase and class Ia ribonucleotide reductases are two enzymes that epitomize such systems where structural insight into their multiple conformations will advance our understanding of their physiological and medically relevant behavior. To meet the technical challenge of investigating these systems, I will exploit the ensemble structural information that can be gained by small- and wide-angle X-ray scattering and employ mathematical methods to deconvolute the mixtures into quantifiable individual states. This work will be complemented by crystallography, spectroscopy, and analytical ultracentrifugation.

瞬时和异质蛋白质相互作用在催化和调节中发挥着重要作用蛋白质复合物和多模块机器的功能。然而，其中涉及的技术挑战此类系统的结构特征为理解其内在设置了关键障碍行为。维生素 B12 依赖性蛋氨酸合酶和 Ia 类核糖核苷酸还原酶是两种体现此类系统的酶将推进对其多种构象的结构洞察我们对他们的生理和医学相关行为的理解。为了应对技术挑战通过研究这些系统，我将利用可以通过小型和小型系统获得的系综结构信息。广角 X 射线散射并采用数学方法将混合物解卷积为可量化的个别国家。这项工作将得到晶体学、光谱学和分析学的补充超速离心。