Advancing Ultraviolet Photodissociation Mass Spectrometry for Precision Mapping of Protein Glycosylation
Advancing Ultraviolet Photodissociation Mass Spectrometry for Precision Mapping of Protein Glycosylation
批准号:
10350600
负责人:
Edwin E Escobar
金额:
$2.77万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-01-01 至 2022-07-31
关键词:
Amino AcidsAtherosclerosisBiochemicalBiologicalC-terminalCell CommunicationCell membraneCell physiologyCellsChemicalsCodeComplexConsensusConsensus SequenceCoupledDefectDevelopmentDiseaseDisease PathwayDissociationEnzymesEpigenetic ProcessEukaryotaEventFunctional disorderGene ProteinsGlycopeptidesGlycoproteinsGlycosidesGoalsGoldHealthHumanImmune responseImmunityIonsKnowledgeLengthLightLinkLocationMalignant NeoplasmsMapsMass Spectrum AnalysisMediatingMessenger RNAMetabolismMethodologyMethodsModificationN-Glycosylation SiteNatureNeoplasm MetastasisPathogenicityPathway interactionsPatternPeptidesPhosphorylationPhotonsPlayPolysaccharidesPositioning AttributePost Translational Modification AnalysisPost-Translational Protein ProcessingProcessProlineProtein GlycosylationProtein-Serine-Threonine KinasesProteinsProteomeProteomicsRNA Polymerase IIRegulationReportingResearchResolutionRoleSamplingSerineSignal TransductionSiteStructureStructure-Activity RelationshipTechniquesThreonineThrombosisTyrosineViralViral Envelope ProteinsVirus Diseasesanalytical methodanalytical toolbaseglycoproteomicsglycosylationhuman diseaseinnovationinsightpolysulfated glycosaminoglycansugartandem mass spectrometrytooltumorultraviolet
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Glycosylation plays a structural and functional role in all fundamental features of proteins in cells. Despite substantial
evidence suggesting O-glycosylation is vital in cellular processes, the nature of O-linked glycans and the specific locations
of O-glycans are not well characterized. To a large extent, the consensus sequence motif N-X-S/T enables reliable
prediction of N-glycosylation sites, but our knowledge of O-glycosylation is hampered by a lack of simple consensus motifs.
As a result, our current understanding of the impact of O-glycosylation is incomplete. A major obstacle to comprehensive
characterization of O-glycosylation by mass spectrometry-based proteomic workflows is the prominent neutral loss of
labile O-linked glycans using conventional collisional activated dissociation, hampering precise localization. Moreover, no
global enzyme exists that can cleave every possible O-glycan β-O-glycosidic linkage, thwarting enzymatic glycomic analysis.
Mass spectrometry coupled with ultraviolet photodissociation (UVPD) is positioned to be an important tool in
glycoproteomics by enabling residue-level resolution of PTMs of proteins implicated in human health. UVPD can be
harnessed to provide simultaneously high sequence coverage of peptides and retention of labile modifications, thus
allowing O-glycan mapping and structural characterization. My development of innovative LC-UVPD-MS strategies suitable
for both targeted and global glycoproteomic applications will provide new insight into the correlation of glycosylation with
disease pathways and drive new biological questions.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
海外基金