Biophysical mechanisms of ABC-F proteins
ABC-F蛋白的生物物理机制
基本信息
- 批准号:9339717
- 负责人:
- 金额:$ 30.76万
- 依托单位:
- 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:2016-09-01 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:ATP phosphohydrolaseATP-Binding Cassette TransportersATPase DomainAntibiotic ResistanceAntibioticsBindingBinding SitesBiochemicalBiologicalBiological AssayBiologyBiophysical ProcessBiophysicsClassificationComplexDiseaseElectron MicroscopyFamilyFamily memberFluorescence SpectroscopyFoundationsGenesGenetic TranslationGenetic studyGenomeGenomicsGoalsHibernationHumanImageKineticsLifeMediatingMessenger RNAMethodsMicrobial Antibiotic ResistanceModelingMolecularMolecular ConformationMonitorNamesPeptidesProcessProtein BiosynthesisProtein FamilyProteinsPublicationsPublishingRegulationResearchRibosomal InteractionRibosomesRoentgen RaysRoleSpecificityStereotypingStructureTestingThermodynamicsTransfer RNATranslatingTranslationsTransmembrane DomainVariantWorkYeastsbiophysical techniquescryogenicsdeep sequencingexperimental studygene functiongenome sequencinggenome-widehuman diseaseinsightmicrobialnovelparalogous geneparticlepeptidyl-tRNAprogramsreconstructionsingle moleculestructural biologytooltranscriptome sequencingtranslation factor
项目摘要
Genome sequencing has revolutionized biology by providing unprecedented insight into the molecular basis
of life. However, it has also established new research challenges. One critical challenge is the elucidation of
the function of uncharacterized protein families, because at least half of the proteins encoded in any genome
lack reliably described biochemical functions. We have attempted to develop systematic approaches to tackle
this problem by combining the tools of structural biology with those of genomics. Using this approach, we
recently elucidated the biochemical function of one of four E. coli proteins belonging to the “ABC-F” sequence
family, which has multiple representatives encoded in all eukaryotic and almost all eubacterial genomes. No
other ABC-F protein had previously had its function characterized in detail, even though published studies
using genome-scale profiling methods have identified the three human paralogs as contributing to a variety of
different diseases. Furthermore, several of the ~30 eubacterial ABC-F paralog groups have been implicated in
mediating microbial antibiotic resistance. Our recently published studies of the E. coli YjjK protein, which we
renamed EttA (Energy-dependent Translational Throttle A), demonstrated that this ABC-F family member is a
regulatory translation factor that mediates hibernation of ribosome initiation complexes dependent on ADP/ATP
ratio. We determined a cryogenic electron microscopy (cryo-EM) structure of EttA trapped in an ATP-bound
state bound to a 70S ribosome, which established that its unprecedented translational control activity is
mediated by binding to a novel factor-binding site between the exit (E) and peptidyl-tRNA-binding (P) tRNA-
binding sites on the ribosome. These studies, together with previous research from the Hunt lab on the
mechanochemistry of homologous ATPases in the ABC Transporter superfamily, suggested that EttA uses a
novel molecular mechanism to sense ADP/ATP ratio, which is a critical monitor of cellular energy status. The
research proposed in this application will harness a wide variety of biochemical, biophysical, and structural
methods to critically evaluate our hypothesis explaining this novel activity while also characterizing the range of
biochemical functions performed by the four ABC-F paralogs expressed by E. coli. These studies will provide
a foundation to understand the biochemical functions of the microbial ABC-F paralogs that confer antibiotic
resistance and the three human ABC-F paralogs, which is critical for understanding their roles in disease.
基因组测序通过提供对分子基础的前所未有的深入了解,彻底改变了生物学
项目成果
期刊论文数量(0)
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JOHN Francis HUNT其他文献
JOHN Francis HUNT的其他文献
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{{ truncateString('JOHN Francis HUNT', 18)}}的其他基金
Rational engineering of improved protein crystallization
改进蛋白质结晶的合理工程
- 批准号:
9767253 - 财政年份:2018
- 资助金额:
$ 30.76万 - 项目类别:
Rational engineering of improved protein crystallization
改进蛋白质结晶的合理工程
- 批准号:
10249105 - 财政年份:2018
- 资助金额:
$ 30.76万 - 项目类别:
SAFETY OF NEBULIZED ISOTONIC SALINE WITH ADDED ALKALINE GLYCINE SOLUTION
添加碱性甘氨酸溶液的雾化等渗盐水的安全性
- 批准号:
8167187 - 财政年份:2010
- 资助金额:
$ 30.76万 - 项目类别:
CRYSTAL STRUCTURES OF B SUBTILIS SECA MUTANTS
枯草芽孢杆菌 SECA 突变体的晶体结构
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7726207 - 财政年份:2008
- 资助金额:
$ 30.76万 - 项目类别:
Structure, mechanism, and inhibition of AlkB homologues
AlkB 同系物的结构、机制和抑制
- 批准号:
7501393 - 财政年份:2007
- 资助金额:
$ 30.76万 - 项目类别:
Structure, mechanism, and inhibition of AlkB homologues
AlkB 同系物的结构、机制和抑制
- 批准号:
7388051 - 财政年份:2007
- 资助金额:
$ 30.76万 - 项目类别:
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