Identifying Key Structural Interactions in Heparan Sulfate-Protein Complexes
鉴定硫酸乙酰肝素-蛋白质复合物中的关键结构相互作用
基本信息
- 批准号:10715985
- 负责人:
- 金额:$ 16.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:Autoimmune DiseasesBindingBinding ProteinsBiologicalBiological ProcessBlood CirculationBlood Coagulation FactorCCL2 geneCXCL10 geneCaliforniaCalorimetryCarbohydratesCatalysisCategoriesCell AdhesionCell Adhesion MoleculesCell CommunicationCell Culture TechniquesCell surfaceCellsCharacteristicsCoagulation ProcessCollaborationsComplexCore ProteinDataDisaccharidesDisease ProgressionDockingDrug TargetingEarly identificationExtracellular MatrixFoundationsFundingFutureGlycosaminoglycansGoalsGrowth FactorHIV-1Heparitin SulfateHispanic-serving InstitutionHumanIL8 geneImmune responseInfectionInfection preventionInflammationIsotope LabelingLibrariesLife Cycle StagesLigandsMammalian CellMembrane ProteinsMethodologyModelingMolecularMolecular ConformationNuclear Magnetic ResonanceProcessProteinsProteoglycanRANTESResearchRoleSignal TransductionSpectrum AnalysisStromal Cell-Derived Factor 1Structural ModelsStructural ProteinStructureSurface Plasmon ResonanceTestingTitrationsTrainingUniversitiesVirusVirus Diseasescell growth regulationchemokinecytokinedrug developmentexperimental analysisextracellularinstitutional capacitynuclear transferprogramsprotein complexreceptorscreeningsugartissue repairundergraduate studentviral entry inhibitorvirtual
项目摘要
Project Summary
Glycosaminoglycans (GAGs), such as heparan sulfate (HS), are important components of the extracellular
matrix of all cells. The extraordinary structural diversity of GAGs enables them to interact with a wide variety of
biological molecules, but primarily proteins, to modulate biological processes, such as cell adhesion, tissue
repair, coagulation, and immune response, among many others. Additionally, a number of different viruses,
including HIV-1, initiate infection of cells by binding to cell surface GAGs. Unfortunately, the diversity of
potential binding motifs in GAG sequences has made identification of relevant sequences challenging. In
particular, heparan sulfate (HS) is the most structurally diverse, with sixteen unique disaccharide configurations
and 256 unique tetrasaccharide configurations. Significant progress has been made in recent years developing
libraries of synthetic HS oligomers, allowing for detailed experimental structural studies of HS-protein
complexes. Understanding the structural basis of these interactions is key to drug development and the HS
binding protein-HS (HSBP-HS) interaction studies to date have been either non-structural or computational.
The overall goal of this project is to utilize these recently developed synthetic HS libraries and NMR-based
structural models to identify key interactions. HIV-1 p17 will be used for initial studies because it is very
important in many stages of the life cycle of HIV-1. Heparan sulfate receptors are known to influence growth
factor signaling, cell adhesion, and enzymatic catalysis on human cells. Thus, this interaction may be one of
the deciding factors for disease progression in humans infected with HIV-1. In Aim 1, a library of synthetic HS
tetrasaccharides will be screened for binding to human immunodeficiency virus type 1 (HIV-1) p17 protein to
identify the sequence-specific HS characteristics of the preferred binding oligomers. In Aim 2, the HSBP-HS
complexes of both strong and weak binding sequences will be studied via nuclear magnetic resonance (NMR)
to model the structure of the complex and identify key interactions for future drug development. After the
methodology is established, HS-binding chemokines will be screened in Aim 3 to identify suitable targets for
future NMR studies.
项目摘要
糖胺聚糖(GAG),如硫酸乙酰肝素(HS),是细胞外基质的重要组分。
所有细胞的矩阵。GAG的非凡结构多样性使它们能够与各种各样的生物分子相互作用。
生物分子,但主要是蛋白质,以调节生物过程,如细胞粘附,组织
修复、凝血和免疫反应等。此外,一些不同的病毒,
包括HIV-1,通过与细胞表面GAG结合来启动细胞感染。不幸的是,
GAG序列中潜在的结合基序使得相关序列的鉴定具有挑战性。在
特别是硫酸乙酰肝素(HS)是结构上最多样化的,具有16种独特的二糖构型
和256种独特的四糖构型。近年来取得了重大进展,
合成HS寡聚体的文库,允许HS蛋白的详细实验结构研究
配合物了解这些相互作用的结构基础是药物开发和HS的关键
迄今为止,结合蛋白-HS(HSBP-HS)相互作用的研究要么是非结构性的,要么是计算性的。
该项目的总体目标是利用这些最近开发的合成HS库和基于NMR的
结构模型,以确定关键的相互作用。HIV-1 p17将用于初步研究,因为它非常
在HIV-1生命周期的许多阶段都很重要。已知硫酸乙酰肝素受体影响生长
因子信号传导、细胞粘附和人类细胞上的酶催化。因此,这种相互作用可以是以下之一:
HIV-1感染者疾病进展的决定因素。在目标1中,合成HS的文库
将筛选四糖与人类免疫缺陷病毒1型(HIV-1)p17蛋白的结合,
鉴定优选结合寡聚体的序列特异性HS特征。在目标2中,HSBP-HS
将通过核磁共振(NMR)研究强结合序列和弱结合序列的复合物
模拟复合物的结构,并确定未来药物开发的关键相互作用。后
方法学建立后,HS结合趋化因子将在目标3中筛选,以确定合适的靶点,
未来的NMR研究
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kari Joanne Pederson其他文献
Kari Joanne Pederson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kari Joanne Pederson', 18)}}的其他基金
NMR studies of vaccinia virus interferon binding protein: interactions with GAGs
痘苗病毒干扰素结合蛋白的 NMR 研究:与 GAG 的相互作用
- 批准号:
8649447 - 财政年份:2014
- 资助金额:
$ 16.27万 - 项目类别:
相似国自然基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:32170319
- 批准年份:2021
- 资助金额:58.00 万元
- 项目类别:面上项目
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:
- 批准年份:2021
- 资助金额:58 万元
- 项目类别:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
- 批准号:31672538
- 批准年份:2016
- 资助金额:62.0 万元
- 项目类别:面上项目
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
- 批准号:31372080
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
P53 binding protein 1 调控乳腺癌进展转移及化疗敏感性的机制研究
- 批准号:81172529
- 批准年份:2011
- 资助金额:58.0 万元
- 项目类别:面上项目
DBP(Vitamin D Binding Protein)在多发性硬化中的作用和相关机制的蛋白质组学研究
- 批准号:81070952
- 批准年份:2010
- 资助金额:35.0 万元
- 项目类别:面上项目
研究EB1(End-Binding protein 1)的癌基因特性及作用机制
- 批准号:30672361
- 批准年份:2006
- 资助金额:24.0 万元
- 项目类别:面上项目
相似海外基金
How lipid binding proteins shape the activity of nuclear hormone receptors
脂质结合蛋白如何影响核激素受体的活性
- 批准号:
DP240103141 - 财政年份:2024
- 资助金额:
$ 16.27万 - 项目类别:
Discovery Projects
Structural classification of NHEJ pathways; unravelling the role of Ku-binding proteins
NHEJ通路的结构分类;
- 批准号:
MR/X00029X/1 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Research Grant
BRC-BIO: Evolutionary Patterns of Ice-Binding Proteins in North Pacific Intertidal Invertebrates
BRC-BIO:北太平洋潮间带无脊椎动物冰结合蛋白的进化模式
- 批准号:
2312378 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Standard Grant
Exploring the roles and functions of sex steroid hormone receptor-associated RNA binding proteins in the development of geriatric diseases.
探索性类固醇激素受体相关 RNA 结合蛋白在老年疾病发展中的作用和功能。
- 批准号:
23K06408 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
UV Plasmon-Enhanced Chiroptical Spectroscopy of Membrane-Binding Proteins
膜结合蛋白的紫外等离子增强手性光谱
- 批准号:
10680969 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Investigating physiologic and pathophysiologic connections between the Parkinson's disease protein alpha-synuclein and RNA binding proteins
研究帕金森病蛋白 α-突触核蛋白和 RNA 结合蛋白之间的生理和病理生理联系
- 批准号:
10744556 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Structural and computational analysis of immune-related RNA-binding proteins
免疫相关 RNA 结合蛋白的结构和计算分析
- 批准号:
23K06597 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Characterization of carbohydrate-binding proteins and their applications
碳水化合物结合蛋白的表征及其应用
- 批准号:
23K05034 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A machine learning approach to identify carbon dioxide-binding proteins for sustainability and health
一种机器学习方法来识别二氧化碳结合蛋白以实现可持续发展和健康
- 批准号:
2838427 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别:
Studentship
The role of RNA binding proteins in heart development and congenital heart defects
RNA结合蛋白在心脏发育和先天性心脏缺陷中的作用
- 批准号:
10827567 - 财政年份:2023
- 资助金额:
$ 16.27万 - 项目类别: