Physiological impact of reduced fidelity in protein synthesis
蛋白质合成保真度降低的生理影响
基本信息
- 批准号:8932246
- 负责人:
- 金额:$ 30.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-10 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAmino Acyl Transfer RNAAmino Acyl-tRNA SynthetasesAminoglycoside AntibioticsAntibioticsAnticodonAttenuatedBacteriaBacteria sigma factor KatF proteinBiochemicalBiochemistryBiophysicsCellsCodon NucleotidesDNADefectDevelopmentEscherichia coliEscherichia coli ProteinsExcisionExhibitsFutureGenesGeneticGoalsGrowthHeat Stress DisordersHeat-Shock ResponseHeatingHost DefenseHydrogen PeroxideHypochloriteKnowledgeLaboratoriesLifeMammalsModelingMolecularMulti-Drug ResistanceMutationNatureNerve DegenerationNutrientOrganismOxidantsOxidative StressPathway interactionsPeptide HydrolasesPeptidesPeroxidesPhysiologicalPlayProcessProtein BiosynthesisProteinsProteomeProteomicsQuality ControlRNA Sequence AnalysisRNA SequencesRNA, Transfer, Amino Acid-SpecificRibosomesRoleSiteSmall RNASourceStagingStarvationStressTestingThreonine-tRNA LigaseTranslational RegulationTranslationsVirus DiseasesWorkYeastsantimicrobialantioxidant enzymebasebiological adaptation to stresscell growth regulationdrug resistant bacteriafitnessgenetic analysisgenetic informationimprovedmitochondrial dysfunctionnext generationnoveloxidationprotein aggregationpublic health relevancestructural biologytooltranscriptome sequencing
项目摘要
DESCRIPTION (provided by applicant): Protein synthesis is a fundamental and essential process in all three domains of life. In the past decades, advances in biochemistry, biophysics, and structural biology have improved our knowledge on the molecular mechanisms of aminoacyl-tRNA (aa-tRNA) synthesis, translational quality control, peptide elongation, and ribosomal decoding. However, we are still at a very early stage of understanding how protein synthesis is regulated in living cells and how translational regulation affects the fitness of different organisms. Protein mistranslation (an increased level of translational errors) has been shown to cause growth defects in bacteria, mitochondrial dysfunction in yeast, and neurodegeneration in mammals. It is therefore commonly accepted that mistranslation is harmful to cells and needs to be avoided. Surprisingly, we and others have shown that mistranslation is increased during oxidative stress and viral infection, leading to a recent proposal that mistranslation may play adaptive roles under certain stress conditions. Experimental evidence to support this model is currently limited, and little is known about these adaptive mechanisms at the molecular level. The objective here is to define how bacteria respond to mistranslation. Specifically, we will (a) determine the mechanism by which mistranslation adapts E. coli to peroxide stress; (b) determine the impact of mistranslation on protein aggregation in E. coli; and (c) define the role of mistranslation caused by oxidative stres in E. coli. Such work will reveal previously unknown adaptive mechanisms by which bacteria survive severe stresses, and improve the knowledge of a new class of translational regulation that enhances phenotypic diversity and fitness through fine-tuning fidelity of protein synthesis.
描述(应用程序提供):蛋白质合成是生命的所有三个领域中的基本和基本过程。在过去的几十年中,生物化学,生物物理学和结构生物学的进步已经提高了我们对氨基酰基-TRNA(AA-tRNA)合成,翻译质量控制,胡椒延长和核糖体解码的了解的知识。但是,我们仍处于了解如何在活细胞中调节蛋白质合成的早期阶段,以及翻译调节如何影响不同组织的适应性。蛋白质误导(翻译误差的水平升高)已显示出细菌的生长缺陷,酵母中的线粒体功能障碍以及哺乳动物的神经变性。因此,通常认为,误导对细胞有害,需要避免。令人惊讶的是,我们和其他人表明,在氧化应激和病毒感染期间,误译增加,导致最近提出的建议,即误译可能在某些应激条件下起适应性作用。目前,支持该模型的实验证据是有限的,对分子水平的这些适应性机制知之甚少。这里的目的是定义细菌对误译的反应。具体而言,我们将(a)确定误导能够使大肠杆菌适应过氧化物应激的机制; (b)确定转移对大肠杆菌中蛋白质聚集的影响; (c)定义了大肠杆菌中氧化菌丝引起的误导的作用。这种工作将揭示以前未知的自适应机制,通过细菌在严重的压力中生存,并提高了新的翻译调节的知识,从而通过蛋白质合成的微调忠诚度增强了表型多样性和适应性。
项目成果
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JIQIANG LING其他文献
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{{ truncateString('JIQIANG LING', 18)}}的其他基金
Regulation and Physiological Roles of Translational Fidelity
翻译保真度的调节和生理作用
- 批准号:
10619629 - 财政年份:2020
- 资助金额:
$ 30.8万 - 项目类别:
Regulation and Physiological Roles of Translational Fidelity
翻译保真度的调节和生理作用
- 批准号:
10725047 - 财政年份:2020
- 资助金额:
$ 30.8万 - 项目类别:
Regulation and Physiological Roles of Translational Fidelity
翻译保真度的调节和生理作用
- 批准号:
10406906 - 财政年份:2020
- 资助金额:
$ 30.8万 - 项目类别:
Regulation and Physiological Roles of Translational Fidelity
翻译保真度的调节和生理作用
- 批准号:
10166886 - 财政年份:2020
- 资助金额:
$ 30.8万 - 项目类别:
Regulation and Physiological Roles of Translational Fidelity
翻译保真度的调节和生理作用
- 批准号:
10617051 - 财政年份:2020
- 资助金额:
$ 30.8万 - 项目类别:
Studies of Aminoacyl-tRNA Synthetase Mutations Causing Progressive Microcephaly
氨酰基-tRNA 合成酶突变导致进行性小头畸形的研究
- 批准号:
9751423 - 财政年份:2018
- 资助金额:
$ 30.8万 - 项目类别:
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