Structure and Function of a novel and pervasive Ubiqitin-binding module

一种新颖且普遍的泛素结合模块的结构和功能

基本信息

批准号：
7578169
负责人：
ROBERT C PIPER
金额：
$ 19.47万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7578169
关键词：
Aging Algorithms Binding Binding Proteins Biological Biological Assay Biological Process Cell physiology Cell surface Cells Chemicals Complex Computers Data Databases Diabetes Mellitus Dimensions Docking Endosomes F-Box Proteins Homeostasis Immunology Inflammation Institutes Knowledge L-Selenomethionine Ligase Maps Mediating Membrane Proteins Metabolism Methods Modeling Molecular Mutagenesis Mutation NMR Spectroscopy Neurobiology Other Finding Play Polyubiquitin Prevalence Process Proteins Public Health Regulation Role Series Solid Sorting - Cell Movement Structure Surface Surveys Techniques Tertiary Protein Structure Testing Ubiquitin Ubiquitination United States National Institutes of Health Work X-Ray Crystallography Yeasts base insight interest multicatalytic endopeptidase complex novel protein degradation protein function receptor trans-Golgi Network ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): One of the ways we can understand how ubiquitin controls various processes is to define the protein interaction modules that can non-covalently bind ubiquitin. Finding such modules within proteins that are already implicated in ubiquitin-dependent processes can uncover new aspects for how these proteins function at the molecular level. Furthermore, finding such modules in other proteins can implicate a role for ubiquitin in processes where it was previously not suspected. We have found that a subset of WD40 beta propellers can bind Ub non covalently. This has led us to hypothesize that many WD40 beta propellers might bind ubiquitin and thus provide new dimension of ubiquitin-dependent control to a variety of biological processes. This proposal will set out to discovery new beta-propellers that bind Ub and discover the structural basis for this interaction. PUBLIC HEALTH RELEVANCE This proposal seeks new knowledge on how ubiquitin might control a wide variety of cellular processes. The work centers on discovering how ubiquitin non- covalently binds to WD40 beta propellers, which are found in many proteins with diverse functions. WD40 beta propeller proteins are involved in aspects of metabolism, diabetes, inflammation, immunology, aging, and neurobiology. This work promises mechanistic insight into how ubiquitin might regulate normal and pathogenic processes, which are of particular interest to many NIH institutes.

描述（由申请人提供）：我们了解泛素如何控制各种过程的方法之一是定义可以非共价结合泛素的蛋白质相互作用模块。在已经涉及泛素依赖性过程的蛋白质中找到此类模块可以揭示这些蛋白质如何在分子水平上发挥作用的新方面。此外，在其他蛋白质中发现此类模块可能暗示泛素在以前未被怀疑的过程中发挥作用。我们发现 WD40 beta 螺旋桨的一个子集可以非共价结合 Ub。这使我们推测许多 WD40 β 螺旋桨可能结合泛素，从而为各种生物过程提供泛素依赖性控制的新维度。该提案将着手发现结合 Ub 的新 β 螺旋桨，并发现这种相互作用的结构基础。公共健康相关性该提案寻求关于泛素如何控制多种细胞过程的新知识。这项工作的重点是发现泛素如何与 WD40 β 螺旋桨非共价结合，WD40 β 螺旋桨存在于许多具有不同功能的蛋白质中。 WD40 β螺旋桨蛋白涉及新陈代谢、糖尿病、炎症、免疫学、衰老和神经生物学等方面。这项工作有望从机制上深入了解泛素如何调节正常和致病过程，这对许多 NIH 研究所特别感兴趣。