Structure and Function of Metabolic Filaments

代谢丝的结构和功能

基本信息

批准号：
10725069
负责人：
Justin M Kollman
金额：
$ 6.61万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10725069
关键词：
6-Phosphofructokinase Allosteric Regulation Biochemical Biological Biological Assay Biological Models Biophysics Carbohydrates Catabolic Process Cells Coupled Critical Pathways Cryoelectron Microscopy DNA Defect Disease Environment Enzymes Equilibrium Failure Filament Funding Glycolysis Grant Growth Homeostasis Human In Vitro Individual Kinetics Lateral Life Ligands Liver Mediating Medical Metabolic Metabolic Control Metabolism Molecular Mutation Neuropathy Nucleotide Biosynthesis Nucleotides Nutrient Pathway interactions Physiological Play Polymers Process Protein Isoforms Pyrimidine RNA Reaction Regulation Ribonucleotides Ribose Role Saccharomycetales Side Speed Stress Structure Tissues Work Yeasts design enzyme activity experimental study glucose metabolism in vivo insight polymerization response self assembly single molecule success sugar

项目摘要

PROJECT SUMMARY Intermediate metabolism must be finely tuned, carefully balanced, and robustly adaptable to changes in environmental conditions. While the individual enzymes that drive most metabolic processes are well understood, only recently has the field come to appreciate the widespread role of metabolic enzyme self- assembly in metabolic organization and control. In particular, we now know that dozens of metabolic enzymes assemble into filamentous structures in vivo and in vitro, and that these filaments act as allosteric effectors to tune enzyme activity. This proposal focuses on self-assembled filaments of metabolic enzymes in glycolysis and nucleotide biosynthesis, processes that extract energy from sugar and generate fundamentally important macromolecular building blocks, respectively. We will use cryo-electron microscopy to determine the structural basis for assembly and regulation, coupled with biochemical, biophysical, and cell biological approaches in an integrative approach to understanding metabolic filament function. This work will provide insight into the specific roles polymerization plays in modulating enzyme function, and illuminate general principles of metabolic control by enzyme filaments.

项目概要中间代谢必须进行精细调整、仔细平衡，并能够强有力地适应环境的变化。环境条件。虽然驱动大多数代谢过程的单个酶都很好据了解，直到最近，该领域才开始认识到代谢酶自我调节的广泛作用。代谢组织和控制中的组装。特别是，我们现在知道数十种代谢酶在体内和体外组装成丝状结构，并且这些丝充当变构效应器调节酶活性。该提案重点关注糖酵解和代谢酶的自组装丝核苷酸生物合成，从糖中提取能量并产生至关重要的过程分别为大分子构件。我们将使用冷冻电子显微镜来确定结构组装和调节的基础，结合生物化学、生物物理和细胞生物学方法了解代谢丝功能的综合方法。这项工作将提供对具体问题的深入了解聚合在调节酶功能中的作用，并阐明代谢控制的一般原理通过酶丝。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments.

耦合结构转变使得人类 CTPS2 丝的高度协同调节成为可能。

DOI：
发表时间：
2020
期刊：
影响因子：
16.8
作者：
Lynch, Eric M;Kollman, Justin M
通讯作者：
Kollman, Justin M

Modular repeat protein sculpting using rigid helical junctions.

使用刚性螺旋连接进行模块化重复蛋白质雕刻。

DOI：
发表时间：
2020-04-21
期刊：
影响因子：
11.1
作者：
Brunette, T J;Bick, Matthew J;Hansen, Jesse M;Chow, Cameron M;Kollman, Justin M;Baker, David
通讯作者：
Baker, David

Filament formation by glutaminase enzymes drives catalysis

谷氨酰胺酶形成丝驱动催化

DOI：
发表时间：
2024-09-14
期刊：
影响因子：
0
作者：
Shi Feng;Cody Aplin;Thuy;R. Cerione
通讯作者：
R. Cerione

Design of biologically active binary protein 2D materials.

生物活性二元蛋白质二维材料的设计。

DOI：
发表时间：
2021-01
期刊：
影响因子：
64.8
作者：
Ben;Watson, Joseph L;Sheffler, William;Johnson, Matthew Camp;Bittleston, Alice;Somasundaram, Logeshwaran;Decarreau, Justin;Jiao, Fang;Chen, Jiajun;Mela, Ioanna;Drabek, Andrew A;Jarrett, Sanchez M;Blacklow, Stephen C;Kaminski
通讯作者：
Kaminski

Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation.

CTP 合酶丝的冷冻电镜结构揭示了芽殖酵母饥饿期间 pH 敏感组装的机制。

DOI：
发表时间：
2021-11-04
期刊：
影响因子：
7.7
作者：
Hansen, Jesse M;Horowitz, Avital;Lynch, Eric M;Farrell, Daniel P;Quispe, Joel;DiMaio, Frank;Kollman, Justin M
通讯作者：
Kollman, Justin M