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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：
8417652
负责人：
Nozomi Ando
金额：
$ 8.55万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
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 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8417652
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 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 meetings prevent protein complex

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：瞬时和非均质蛋白质相互作用在蛋白质复合物和多模块机器的催化和调节功能中发挥重要作用。然而，这些系统的结构特征所涉及的技术挑战对理解其内在行为设置了关键障碍。维生素b12依赖的蛋氨酸合成酶和Ia类核糖核苷酸还原酶是这类系统的两种酶的缩影，对其多种构象的结构洞察将促进我们对其生理和医学相关行为的理解。为了应对研究这些系统的技术挑战，我将利用可通过小角度和广角x射线散射获得的系综结构信息，并采用数学方法将混合物反卷积成可量化的单个状态。这项工作将辅以晶体学、光谱学和分析性超离心。