Determining the scope of prenylatable protein sequences
确定可异戊二烯化的蛋白质序列的范围
基本信息
- 批准号:10461733
- 负责人:
- 金额:$ 38.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-20 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAmino Acid SequenceAmino AcidsBeliefBiochemicalBioinformaticsBiologicalBiologyCENP-E proteinChargeComplexConsensusCoupledCysteineDataDiseaseEnzymesFrequenciesGeneticGuanosine Triphosphate PhosphohydrolasesHumanIn VitroInvestigationKnowledgeLeadMachine LearningMediatingMembraneMethodsMethylationModificationMolecularMolecular ChaperonesMonitorNuclear LaminOnline SystemsPartner in relationshipPathway interactionsPhenotypePheromonePhosphotransferasesPositioning AttributePost Translational Modification AnalysisPost-Translational Protein ProcessingPrevalencePropertyProtein FarnesylationProteinsProteolysisReporterReportingResearchShapesSpecificityTestingTherapeuticUrsidae FamilyYeastsbasebiophysical analysisfarnesylationgenetic selectionin vivoisoprenylationnext generation sequencingprediction algorithmpreventprotein farnesyltransferaseprotein functionprotein geranylgeranyltransferaseprotein protein interactionras-Related G-Proteins
项目摘要
PROJECT SUMMARY
This study investigates the specificity of farnesyl transferase (FTase) that isoprenylates CaaX proteins.
Studies probing the in vivo activity of the FTase have historically used reporters (e.g. Ras GTPases) that
undergo complex multi-step post-translational modification (PTM), involving initial farnesylation followed by
CaaX proteolysis and carboxyl methylation. This study takes advantage of Hsp40 Ydj1, a farnesylation-only
reporter for which we have developed a range of methods to monitor its PTM status. Its use reveals that
farnesylation is not necessarily coupled to subsequent PTMs as has been generally accepted for CaaX
proteins, and that FTase specificity is significantly more promiscuous than anticipated. These findings
challenge the conventional paradigm for how farnesylated proteins are modified and which proteins are
targeted by FTase. We will extend our studies to fully resolve the specificity of FTase using a combination of
genetic, biochemical, bioinformatic, and biophysical studies. We bring to bear on our investigations an
exceptionally strong set of preliminary findings, the complementary expertise of several research groups, and a
comprehensive molecular toolbox for the study of farnesylated proteins and other enzymes associated with this
post-translational modification pathway.
项目总结
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A comprehensive in vivo screen of yeast farnesyltransferase activity reveals broad reactivity across a majority of CXXX sequences.
- DOI:10.1093/g3journal/jkad094
- 发表时间:2023-07-05
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Functional classification and validation of yeast prenylation motifs using machine learning and genetic reporters.
- DOI:10.1371/journal.pone.0270128
- 发表时间:2022
- 期刊:
- 影响因子:3.7
- 作者:
- 通讯作者:
Specific Disruption of Ras2 CAAX Proteolysis Alters Its Localization and Function.
- DOI:10.1128/spectrum.02692-22
- 发表时间:2023-02-14
- 期刊:
- 影响因子:3.7
- 作者:
- 通讯作者:
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Natarajan Kannan其他文献
Natarajan Kannan的其他文献
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{{ truncateString('Natarajan Kannan', 18)}}的其他基金
Annotating dark ion-channel functions using evolutionary features, machine learning and knowledge graph mining
使用进化特征、机器学习和知识图挖掘注释暗离子通道函数
- 批准号:
10457684 - 财政年份:2022
- 资助金额:
$ 38.67万 - 项目类别:
Annotating dark ion-channel functions using evolutionary features, machine learning and knowledge graph mining (Kennady Boyd)
使用进化特征、机器学习和知识图挖掘注释暗离子通道函数 (Kennady Boyd)
- 批准号:
10809950 - 财政年份:2022
- 资助金额:
$ 38.67万 - 项目类别:
Annotating dark ion-channel functions using evolutionary features, machine learning and knowledge graph mining
使用进化特征、机器学习和知识图挖掘注释暗离子通道函数
- 批准号:
10661550 - 财政年份:2022
- 资助金额:
$ 38.67万 - 项目类别:
Annotating dark ion-channel functions using evolutionary features, machine learning and knowledge graph mining (Rayna Carter)
使用进化特征、机器学习和知识图挖掘注释暗离子通道函数 (Rayna Carter)
- 批准号:
10809931 - 财政年份:2022
- 资助金额:
$ 38.67万 - 项目类别:
Unlocking sequence-structure-function-disease relationships in large protein super-families
解锁大型蛋白质超家族中的序列-结构-功能-疾病关系
- 批准号:
10793016 - 财政年份:2021
- 资助金额:
$ 38.67万 - 项目类别:
Unlocking sequence-structure-function-disease relationships in large protein super-families
解锁大型蛋白质超家族中的序列-结构-功能-疾病关系
- 批准号:
10552630 - 财政年份:2021
- 资助金额:
$ 38.67万 - 项目类别:
Determining the scope of prenylatable protein sequences
确定可异戊二烯化的蛋白质序列的范围
- 批准号:
10019396 - 财政年份:2019
- 资助金额:
$ 38.67万 - 项目类别:
A data analytics framework for mining the dark kinome
用于挖掘暗激酶组的数据分析框架
- 批准号:
9915864 - 财政年份:2019
- 资助金额:
$ 38.67万 - 项目类别:
Determining the scope of prenylatable protein sequences
确定可异戊二烯化的蛋白质序列的范围
- 批准号:
10218213 - 财政年份:2019
- 资助金额:
$ 38.67万 - 项目类别:
A data analytics framework for mining the dark kinome
用于挖掘暗激酶组的数据分析框架
- 批准号:
10348826 - 财政年份:2019
- 资助金额:
$ 38.67万 - 项目类别:
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