The structural dynamics of ribosomal frameshifting and ribosome rescue
核糖体移码和核糖体拯救的结构动力学
基本信息
- 批准号:10578684
- 负责人:
- 金额:$ 39.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAmino AcidsAntibioticsBacteriaBacterial ModelBindingBiochemicalBiologicalBiotechnologyClinicalCodon NucleotidesCollaborationsComplementCryoelectron MicroscopyDataDevelopmentDiseaseEukaryotaEventFluorescenceFrameshift MutationGene ExpressionGenomeGoalsHealthHumanIn VitroInvestigationKineticsLabelLaboratoriesLettersLifeLinkMalignant NeoplasmsMediatingMessenger RNAModelingMolecular ConformationMolecular TargetMotivationNucleotidesOrganismPhysiologicalPlayPositioning AttributeProcessProductionPropertyProtein BiosynthesisProtein TruncationProteinsReportingResolutionRestRibosomal FrameshiftingRibosomal ProteinsRibosomesRoleSaccharomyces cerevisiaeSeriesSignal TransductionSpecific qualifier valueStructureSystemTechniquesTechnologyTestingTimeTransfer RNATranslationsViral CancerVirus DiseasesWorkYeastsexperimental studyflexibilityfluorescence imagingfluorophorehuman diseasenext generationpolypeptidepublic health relevancereconstitutionsingle moleculesingle-molecule FRETsmall moleculesmall molecule therapeutics
项目摘要
PROJECT SUMMARY
Translation of messenger RNAs (mRNAs) into proteins by the ribosome and the rest of the translation
machinery (TM) is a fundamental step in gene expression that is central to life. Because the bacterial TM is a
proven target for the development of new antibiotics and because many human diseases have been causally
linked to dysregulation of translation, the mechanisms of translation and translational control in bacteria and
eukaryotes remain under intense investigation. Over the past two decades, structural studies have revealed
the large-scale structural rearrangements the TM undergoes during protein synthesis. Unfortunately, the size,
complexity, and conformational flexibility of the TM have greatly impeded studies of these dynamics,
significantly limiting our understanding of how these dynamics contribute to the mechanisms of translation and
translational control. Nonetheless, using a combination of single-moleucle fluorescence and structural
techniques, we and others have been able to characterize the dynamics of the core steps of translation by the
bacterial TM. Despite these accomplishments, critical gaps in our understanding remain regarding whether and
how the dynamics of these core steps are modulated as part of biomedically important translational control
strategies. To fill these gaps, in the first aim of this application, we propose to use a combination of single-
molecule fluorescence, structural, and biochemical approaches to investigate how the dynamics of the
bacterial TM are modulated in order to drive ribosomal frameshifting. Frameshifting is a translational control
strategy in which the TM slips backward or forward by one or more nucleotides on the mRNA to either correct
an insertion or deletion ‘frameshift’ mutation that would otherwise result in production of an aberrant or
truncated protein or to drive the synthesis of more than one protein product from a single mRNA. These
experiments promise to reveal the still-elusive mechanism(s) that underlie frameshifting. In the second aim, we
will use analogous approaches to investigate how ribosome rescue factors modulate the dynamics of the
bacterial TM as part of the mechanisms through which they recognize and rescue ribosomes that have
become translationally compromised. These studies will provide structure-based mechanistic models of
bacterial ribosome rescue systems that can be exploited in the development of new antibiotics. In the third aim,
we will extend our combination of single-molecule fluorescence and structural techniques to a yeast translation
system, enabling us to investigate eukaryotic-specific aspects of the core steps of translation, frameshifting,
and ribosome rescue. The results of these studies will reveal the mechanisms that drive and regulate
translation in eukaryotes, providing a framework for investigating the role of translational control in human
health and disease.
项目总结
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 }}
Ruben L Gonzalez其他文献
Ruben L Gonzalez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('Ruben L Gonzalez', 18)}}的其他基金
Dynamics and mechanism of sodium-dependent carboxylate transporters
钠依赖性羧酸转运蛋白的动力学和机制
- 批准号:
10577283 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
The mechanism and regulation of mRNA recruitment during eukaryotic translation initiation
真核翻译起始过程中mRNA招募的机制和调控
- 批准号:
10578362 - 财政年份:2022
- 资助金额:
$ 39.36万 - 项目类别:
Combined Optical Tweezers-Fluorescence Super-Resolution Microscope for Single-Molecule Biophysical Studies
用于单分子生物物理研究的光镊-荧光超分辨率组合显微镜
- 批准号:
10177000 - 财政年份:2021
- 资助金额:
$ 39.36万 - 项目类别:
The structural dynamics of ribosomal frameshifting and ribosome rescue
核糖体移码和核糖体拯救的结构动力学
- 批准号:
10377976 - 财政年份:2020
- 资助金额:
$ 39.36万 - 项目类别:
Studies of Riboswitch-Mediated Transcriptional Control Using Single-Molecule Fiel
利用单分子场进行核糖开关介导的转录控制的研究
- 批准号:
8695928 - 财政年份:2014
- 资助金额:
$ 39.36万 - 项目类别:
Studies of Riboswitch-Mediated Transcriptional Control Using Single-Molecule Fiel
利用单分子场进行核糖开关介导的转录控制的研究
- 批准号:
8860202 - 财政年份:2014
- 资助金额:
$ 39.36万 - 项目类别:
The Structural Dynamics of Translation Initiation
翻译起始的结构动力学
- 批准号:
10011816 - 财政年份:2008
- 资助金额:
$ 39.36万 - 项目类别:
相似海外基金
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 39.36万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 39.36万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Design and Synthesis of Fluorescent Amino Acids: Novel Tools for Biological Imaging
荧光氨基酸的设计与合成:生物成像的新工具
- 批准号:
2888395 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Studentship
Collaborative Research: RUI: Elucidating Design Rules for non-NRPS Incorporation of Amino Acids on Polyketide Scaffolds
合作研究:RUI:阐明聚酮化合物支架上非 NRPS 氨基酸掺入的设计规则
- 批准号:
2300890 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Continuing Grant
Structurally engineered N-acyl amino acids for the treatment of NASH
用于治疗 NASH 的结构工程 N-酰基氨基酸
- 批准号:
10761044 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial
生活方式、支链氨基酸和心血管危险因素:一项随机试验
- 批准号:
10728925 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别:
Single-molecule protein sequencing by barcoding of N-terminal amino acids
通过 N 端氨基酸条形码进行单分子蛋白质测序
- 批准号:
10757309 - 财政年份:2023
- 资助金额:
$ 39.36万 - 项目类别: