Structural Robustness of Ribosome Functional Centers
Structural Robustness of Ribosome Functional Centers
批准号:
10693898
负责人:
Steven Gregory
金额:
$36.07万
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
项目状态:
未结题
起止时间:
2010-09-15 至 2025-08-31
关键词:
Active SitesAddressAffectAmino Acid SubstitutionAntibiotic ResistanceAntibioticsBindingBinding SitesBiochemistryBiologicalCapromycinCodon NucleotidesCollaborationsCollectionComplexCryoelectron MicroscopyCrystal FormationDataDependenceDevelopmentDrug DesignElementsEquilibriumEvolutionFutureGene ExpressionGeneticGenetic studyGoalsHeadHealthHumanInvestigationLaboratoriesMethodsMolecularMolecular BiologyMolecular ConformationMolecular MachinesMotionMovementMutationNatureOutcomePhenotypePositioning AttributeProtein BiosynthesisPublicationsResistanceResolutionRibosomal ProteinsRibosomal RNARibosomesRoleRotationSignal PathwaySignal TransductionSiteSpectinomycinStreptomycinStructureStructure-Activity RelationshipTransfer RNAVisualizationWorkX-Ray Crystallographyantimicrobial drugfightingfitnessinsightmutantnovelpreventresistance mechanismresistance mutationstructural biology
中文摘要
项目总结
英文摘要
Project Summary
The ribosome is the macromolecular machine, conserved throughout evolution, that is
responsible for the synthesis of proteins and is therefore a fundamental component of gene
expression. Because of its central role in biochemistry, the ribosome has become the target of
more than half of all antibiotics, and the evolution of antibiotic resistance due to mutations in the
ribosome has become a major threat to human health. Understanding the molecular basis of
antibiotic resistance therefore has significant implications for the fight against the threat of
resistance. In deciphering the mechanism of antibiotic resistance, fundamental insights into the
mechanism of ribosome function can also be acquired, leading to possible novel antimicrobial
agents through rational drug design. Through an ongoing collaborative effort, this proposal
capitalizes on the ability of the PIs to combine genetics and structural biology to address
fundamental questions of ribosome structure and function and provide a framework for future
development of novel antimicrobial agents. The Aims of this proposal are: (1) Dissect 30S subunit
conformational dynamics during tRNA movement through the ribosome; (2) Define the role of two
intersubunit bridges in 30S-50S rotation during translocation; (3) Determine the structural basis
for signaling pathways through the ribosome.
Achieving these aims will involve exploiting the expertise of the three PIs to generate and
characterize functionally impactful mutants and determine their structures by X-ray
crystallography or cryo-electron microscopy. The strengths of our proposal include: (1) extensive
expertise in the experimental methods to be applied; (2) a long track record of effective
collaboration between the PIs; (3) an extensive publication track record in the field of ribosome
structure and function; (4) a large volume of preliminary data and ongoing studies, including
multiple studies nearing completion. Accomplishing these goals will significantly advance the field
by answering long-standing questions about antibiotic resistance mechanisms, while
simultaneously expanding our understanding of the basic underlying mechanism of the ribosome.
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DOI:
10.1038/s41589-020-00715-0
发表时间:
2021-04
期刊:
Nature chemical biology
影响因子:
14.8
作者:
[Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, Polikanov YS]
通讯作者:
Polikanov YS
The C-terminus of ribosomal protein uS4 contributes to small ribosomal subunit biogenesis and the fidelity of translation.
核糖体蛋白 uS4 的 C 末端有助于小核糖体亚基的生物发生和翻译的保真度。
DOI:
10.1016/j.biochi.2017.05.004
发表时间:
2017
期刊:
Biochimie
影响因子:
3.9
作者:
[Kamath,Divya, Allgeyer,BenjaminB, Gregory,StevenT, Bielski,MargaretC, Roelofsz,DavidM, Sabapathypillai,SharonL, Vaid,Nikhil, O'Connor,Michael]
通讯作者:
O'Connor,Michael
Alterations in the ribosomal protein bL12 of E. coli affecting the initiation, elongation and termination of protein synthesis.
大肠杆菌核糖体蛋白 bL12 的改变影响蛋白质合成的起始、延伸和终止。
DOI:
10.1016/j.biochi.2020.06.006
发表时间:
2020
期刊:
Biochimie
影响因子:
3.9
作者:
[Younkin,AdamD, Gregory,StevenT, O'Connor,Michael]
通讯作者:
O'Connor,Michael
Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion.
Cfr 介导的抗菌素耐药性的结构基础及其逃避机制。
DOI:
10.1101/2023.09.27.559749
发表时间:
2023
期刊:
bioRxiv : the preprint server for biology
影响因子:
--
作者:
[Aleksandrova,ElenaV, Wu,KelvinJY, Tresco,BenIC, Syroegin,EgorA, Killeavy,ErinE, Balasanyants,SamsonM, Svetlov,MaximS, Gregory,StevenT, Atkinson,GemmaC, Myers,AndrewG, Polikanov,YuryS]
通讯作者:
Polikanov,YuryS
DOI:
10.1007/s00792-014-0663-8
发表时间:
2015-01
期刊:
EXTREMOPHILES
影响因子:
2.9
作者:
[Carr, Jennifer F., Gregory, Steven T., Dahlberg, Albert E.]
通讯作者:
Dahlberg, Albert E.
共 11 条
Structural Robustness of Ribosome Functional Centers
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批准号:9266791
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项目类别:
-
资助金额:$34.73万
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财政年份:2010
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负责人:Steven Gregory
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依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:10297234
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项目类别:
-
资助金额:$38.69万
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财政年份:2010
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负责人:Steven Gregory
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依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:8537942
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项目类别:
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资助金额:$29.41万
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财政年份:2010
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负责人:Steven Gregory
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依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:10478082
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项目类别:
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资助金额:$36.04万
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财政年份:2010
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负责人:Steven Gregory
-
依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:8726425
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项目类别:
-
资助金额:$30.47万
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财政年份:2010
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负责人:Steven Gregory
-
依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:8325081
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项目类别:
-
资助金额:$30.47万
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财政年份:2010
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负责人:Steven Gregory
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依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:8142818
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项目类别:
-
资助金额:$30.47万
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财政年份:2010
-
负责人:Steven Gregory
-
依托单位:
Structural Robustness of Ribosome Functional Centers
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批准号:7944383
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项目类别:
-
资助金额:$30.78万
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财政年份:2010
-
负责人:Steven Gregory
-
依托单位:
海外基金