Studies on Protein Lipidation
蛋白质脂化研究
基本信息
- 批准号:9707092
- 负责人:
- 金额:$ 7.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-08-01 至 2020-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcyltransferaseAddressAlkynesAnimal ModelAntiviral AgentsApplications GrantsBacteriaBiochemicalBioinformaticsBiologicalBiological AssayBiologyCell LineCellsCellular biologyChemicalsComplexCysteineDendritic CellsDetectionEukaryotaFatty AcidsGenomicsGoalsGrantHost DefenseHost resistanceHumanImmunityIn VitroInfectionInfluenza A virusIntegral Membrane ProteinIntegration Host FactorsInterferonsLabelLaboratoriesLifeLigationLipidsMammalian CellMembraneMetabolicMethodsMusPalmitic AcidsPathway interactionsPhenotypeProtein AnalysisProtein BiochemistryProtein IsoformsProtein SProteinsProteomicsReagentReporterResistanceRoleSeriesSignal PathwaySiteVirus DiseasesYeastsbasebiophysical analysiscell typecombatesterasefatty acylationinfluenzavirusmicrobialmutantnovelpalmitoylationpredictive toolsreconstitutiontool
项目摘要
PROJECT SUMMARY
Lipid chemical reporters and bioorthogonal ligation methods developed by my laboratory have provided new
opportunities to investigate the functions of lipid-modified proteins in biology. Our proteomic analysis of fatty-
acylated proteins in dendritic cells using fatty acid chemical reporters and bioorthogonal chemical proteomics
has revealed a new role for protein S-fatty-acylation in host defense against viral infections. We discovered
that S-fatty-acylation of membrane-proximal cysteines on murine IFITM3 is crucial for its membrane
localization and antiviral activity against influenza A virus. The mechanisms that control S-fatty-acylation of
human IFITM proteins have not been evaluated and will be addressed in this grant proposal. Aim 1 will
evaluate the S-fatty-acylation levels, sites and function of human IFITM isoforms in different cell types/states of
activation. Aim 2 describes the characterization of fatty acids covalently attached to human IFITM3 in cells.
Aim 3 describes site-specific lipidation and reconstitution of IFITM3 in vitro for detailed biochemical and
biophysical studies. Determining the mechanisms that control S-fatty-acylation IFITM3 function is crucial for
understanding host immunity and may reveal new strategies for combatting virus infection in humans. The
chemical approaches described in this grant should provide new reagents and methods for studying fatty-
acylated proteins.
项目总结
我实验室开发的脂类化学报告和生物正交连接方法提供了新的
研究脂质修饰蛋白质在生物学中的功能的机会。我们对脂肪的蛋白质组学分析-
用脂肪酸化学报告和生物正交化学蛋白质组学研究树突状细胞中的酰化蛋白
揭示了蛋白质S在宿主防御病毒感染中的新作用-脂肪酰化。我们发现
膜-近端半胱氨酸的S-脂肪酰化对小鼠IFITM3膜的影响
甲型流感病毒的定位和抗病毒活性。S-脂肪酰化的调控机制
人类IFITM蛋白还没有被评估,将在这项赠款提案中讨论。目标1将
评价不同细胞类型/状态下人IFITM异构体的S-脂肪酰化水平、位点和功能
激活。目的2描述细胞内与人IFITM3共价结合的脂肪酸的特性。
目的3描述IFITM3在体外的位点特异性脂化和重组,以进行详细的生化和
生物物理学研究。确定控制S-脂肪酰化IFITM3功能的机制对于
了解宿主免疫,并可能揭示抗击人类病毒感染的新策略。这个
这项资助中描述的化学方法应该为研究脂肪的化学方法提供新的试剂和方法。
酰化蛋白质。
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)
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Howard C Hang其他文献
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{{ truncateString('Howard C Hang', 18)}}的其他基金
Microbiota, Probiotic and Dietary Metabolite Control of Enteric Pathogen Virulence
微生物群、益生菌和膳食代谢物对肠道病原体毒力的控制
- 批准号:
10562497 - 财政年份:2022
- 资助金额:
$ 7.87万 - 项目类别:
Distal gut microbiome targets of host anti-proteolytic proteins during colitis
结肠炎期间宿主抗蛋白水解蛋白的远端肠道微生物组目标
- 批准号:
10320030 - 财政年份:2020
- 资助金额:
$ 7.87万 - 项目类别:
Translation of commensal bacteria mechanism for immunotherapy
共生菌免疫治疗机制的转化
- 批准号:
10311095 - 财政年份:2019
- 资助金额:
$ 7.87万 - 项目类别:
Translation of commensal bacteria mechanism for immunotherapy
共生菌免疫治疗机制的转化
- 批准号:
10533309 - 财政年份:2019
- 资助金额:
$ 7.87万 - 项目类别:
Translation of commensal bacteria mechanism for immunotherapy
共生菌免疫治疗机制的转化
- 批准号:
10064132 - 财政年份:2019
- 资助金额:
$ 7.87万 - 项目类别:
Translation of commensal bacteria mechanism for immunotherapy
共生菌免疫治疗机制的转化
- 批准号:
10379772 - 财政年份:2019
- 资助金额:
$ 7.87万 - 项目类别:
Elucidation of Commensal Bacteria Mechanisms Required for Host Protection
阐明宿主保护所需的共生细菌机制
- 批准号:
9894505 - 财政年份:2013
- 资助金额:
$ 7.87万 - 项目类别:
Elucidation of Commensal Bacteria Mechanisms Required for Host Protection
阐明宿主保护所需的共生细菌机制
- 批准号:
8594254 - 财政年份:2013
- 资助金额:
$ 7.87万 - 项目类别:
Elucidation of Commensal Bacteria Mechanisms Required for Host Protection
阐明宿主保护所需的共生细菌机制
- 批准号:
8412902 - 财政年份:2013
- 资助金额:
$ 7.87万 - 项目类别:
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