Structural and Functional Analysis of Nucleocytoplasmic Protein O-Glycosyltransferases in Plants
植物核胞质蛋白 O-糖基转移酶的结构和功能分析
基本信息
- 批准号:10648930
- 负责人:
- 金额:$ 41.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgricultureAllosteric RegulationAnabolismAnimalsArabidopsisBacteriaBindingBiochemicalBiological AssayBiologyCell physiologyCellsComplexCryoelectron MicroscopyDefectDiabetes MellitusDiseaseEnvironmentEnzymesEventFamilyFucosyltransferaseGenesGeneticGenetic TranscriptionGibberellinsGrowthGuanosine Diphosphate FucoseHealthHumanIndividualInsectaKnowledgeLengthLifeLinkMalignant NeoplasmsMediatingMetabolicModificationMolecularMolecular ConformationMutationN-terminalNeurodegenerative DisordersO-GlcNAc transferaseOrganismPhenotypePhytochromePlant Growth RegulatorsPlantsPlayProtein GlycosylationProteinsProteomeProteomicsPublic HealthRegulationResistanceRoleSequence HomologySignal PathwaySignal TransductionSite-Directed MutagenesisStructureSubstrate SpecificityTranscription Factor 3Transcription RepressorVariantVirulenceenvironmental changegene conservationgenetic analysisglycosylationglycosyltransferasehuman diseaseinsightlink proteinmutantnanobodiesnovelparalogous geneplant growth/developmentpublic health relevanceresponsesugartooltranscription factortranscriptional reprogramming
项目摘要
Project Summary/Abstract
O-linked protein glycosylation orchestrates diverse signaling events in plant development in response to the
changing environment. We have discovered the first nucleocytoplasmic O-fucosyltransferase, SPINDLY (SPY)
in Arabidopsis, which together with its paralog SECRET AGENT (SEC), an O-GlcNAc transferase (OGT), post-
translationally modify the conserved DELLA family of transcription regulators, such as RGA, to control their ability
to modulate multiple signaling pathways. SPY-catalyzed O-fucosylation of RGA enhances the RGA interaction
with key transcription factors to suppress plant growth, whereas SEC-mediated O-GlcNAcylation weakens RGA
activity and promotes plant development. Despite their functional significance, how these two homologous
glycosyltransferases, SPY and SEC, have evolved distinct substrate specificities and how these two types of
glycosylation, O-fucosylation by SPY and O-GlcNAcylation by SEC, regulate the RGA conformation to influence
plant development at the molecular level have remained unknown. We propose to elucidate the molecular details
of SPY, SEC, and their substrate and product complexes, as well as the distinct structural and functional
consequences of RGA O-fucosylation and O-GlcNAcylation. Recent proteomic analysis has unveiled hundreds
of SPY and SEC substrates beyond RGA, highlighting the broad implication of protein glycosylation in regulating
cellular functions. In order to overcome the potential pleotropic effects brought by spy and sec mutations in planta
and decipher the functional consequences of O-fucosylation and O-GlcNAcylation for specific target proteins,
we will develop nanobody-fused SPY and SEC variants for precise target modification. Collectively, our study
will fill the critical knowledge gap about the structural and functional consequences of protein glycosylation in
plants. As SPY-like genes are conserved in diverse organisms, including plants, bacteria, and parasitic protists,
and as SEC-like (OGT) genes are broadly distributed in plants and animals, a molecular understanding of these
enzymes and their distinct structural and functional consequences will have a profound impact in plant biology,
agriculture, and human health and diseases.
项目概要/摘要
O-连接蛋白糖基化协调植物发育中的多种信号事件,以响应
不断变化的环境。我们发现了第一个核质 O-岩藻糖基转移酶 SPINDLY (SPY)
在拟南芥中,它与它的旁系同源物 SECRET AGENT (SEC) 一起,是一种 O-GlcNAc 转移酶 (OGT),
翻译修饰保守的 DELLA 转录调节因子家族,例如 RGA,以控制其能力
调节多种信号通路。 SPY 催化的 RGA O-岩藻糖基化增强了 RGA 相互作用
具有抑制植物生长的关键转录因子,而 SEC 介导的 O-GlcNAc 酰化会削弱 RGA
活性并促进植物发育。尽管它们具有重要的功能,但这两个同源物如何
糖基转移酶 SPY 和 SEC 已进化出不同的底物特异性,以及这两种类型如何
糖基化、SPY 的 O-岩藻糖基化和 SEC 的 O-GlcNA 酰化,调节 RGA 构象以影响
分子水平上的植物发育仍然未知。我们建议阐明分子细节
SPY、SEC 及其底物和产物复合物,以及独特的结构和功能
RGA O-岩藻糖基化和 O-GlcNAcylation 的后果。最近的蛋白质组学分析揭示了数百个
RGA 之外的 SPY 和 SEC 底物,强调了蛋白质糖基化在调节中的广泛含义
细胞功能。为了克服植物中spy和sec突变带来的潜在多效性效应
并破译 O-岩藻糖基化和 O-GlcNAcNA 酰化对特定靶蛋白的功能影响,
我们将开发纳米抗体融合的 SPY 和 SEC 变体,以实现精确的目标修饰。总的来说,我们的研究
将填补关于蛋白质糖基化的结构和功能后果的关键知识空白
植物。由于 SPY 样基因在多种生物体中保守,包括植物、细菌和寄生原生生物,
由于 SEC 样(OGT)基因广泛分布于植物和动物中,因此对这些基因的分子理解
酶及其独特的结构和功能后果将对植物生物学产生深远的影响,
农业、人类健康和疾病。
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)
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Tai-Ping Sun其他文献
Tai-Ping Sun的其他文献
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{{ truncateString('Tai-Ping Sun', 18)}}的其他基金
Structure and Function Analyses of DELLA Interacting Proteins in Arabidopsis
拟南芥中 DELLA 相互作用蛋白的结构和功能分析
- 批准号:
8515471 - 财政年份:2012
- 资助金额:
$ 41.92万 - 项目类别:
Functional Analysis of Protein O-Glycosylation in Regulating Nuclear Growth Repressor DELLA and Plant Development in Arabidopsis
拟南芥核生长抑制因子 DELLA 蛋白 O-糖基化调节及植物发育的功能分析
- 批准号:
9899248 - 财政年份:2012
- 资助金额:
$ 41.92万 - 项目类别:
Structure and Function Analyses of DELLA Interacting Proteins in Arabidopsis
拟南芥中 DELLA 相互作用蛋白的结构和功能分析
- 批准号:
8372892 - 财政年份:2012
- 资助金额:
$ 41.92万 - 项目类别:
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