2023
Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
Chongsaritsinsuk J, Steigmeyer A, Mahoney K, Rosenfeld M, Lucas T, Smith C, Li A, Ince D, Kearns F, Battison A, Hollenhorst M, Judy Shon D, Tiemeyer K, Attah V, Kwon C, Bertozzi C, Ferracane M, Lemmon M, Amaro R, Malaker S. Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE. Nature Communications 2023, 14: 6169. PMID: 37794035, PMCID: PMC10550946, DOI: 10.1038/s41467-023-41756-y.Peer-Reviewed Original ResearchConceptsFamily of proteinsMucin domainO-glycosylationBiological functionsKey regulatorComplex glycansMass spectrometric analysisFunctional relevanceTIM familyDetailed molecular structureCritical roleGlycosylationProteinSpectrometric analysisStructural featuresUnique abilityStructural dynamicsMolecular dynamics simulationsTim-3 functionFamilyPowerful workflowRegulatorImmune cellsCheckpointGlycansDesign of a mucin-selective protease for targeted degradation of cancer-associated mucins
Pedram K, Shon D, Tender G, Mantuano N, Northey J, Metcalf K, Wisnovsky S, Riley N, Forcina G, Malaker S, Kuo A, George B, Miller C, Casey K, Vilches-Moure J, Ferracane M, Weaver V, Läubli H, Bertozzi C. Design of a mucin-selective protease for targeted degradation of cancer-associated mucins. Nature Biotechnology 2023, 42: 597-607. PMID: 37537499, PMCID: PMC11018308, DOI: 10.1038/s41587-023-01840-6.Peer-Reviewed Original ResearchCancer progressionSpecific protein glycoformsUndruggable proteinsTargeted degradationProtein degradationBreast cancer progressionCell surface bindingSubstrate selectivityCell-type selectivityCell deathGlycan motifsProtein glycoformsDiscrete peptidesCancer cellsProteinCulture modelProteaseTarget cellsTumor growthCancer-associated mucinsCellsMouse modelDegradersGrowthMotif
2022
A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond
Medley BJ, Leclaire L, Thompson N, Mahoney KE, Pluvinage B, Parson MAH, Burke JE, Malaker S, Wakarchuk W, Boraston AB. A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond. Journal Of Biological Chemistry 2022, 298: 102439. PMID: 36049519, PMCID: PMC9513282, DOI: 10.1016/j.jbc.2022.102439.Peer-Reviewed Original ResearchConceptsUncharacterized proteinsCarbohydrate-binding moduleHuman gut microbiotaHost adaptationSubstrate recognitionCatalytic motifN-terminalHost healthGut environmentPeptidase activityHost mucinsNutrient sourceAkkermansia muciniphilaEnzymeKey membersPeptide bondProteinBacteriumActive siteGut microbiotaTn antigenPeptide backboneGenesMicrobesGlycoproteomics
Bagdonaite I, Malaker S, Polasky D, Riley N, Schjoldager K, Vakhrushev S, Halim A, Aoki-Kinoshita K, Nesvizhskii A, Bertozzi C, Wandall H, Parker B, Thaysen-Andersen M, Scott N. Glycoproteomics. Nature Reviews Methods Primers 2022, 2: 48. DOI: 10.1038/s43586-022-00128-4.Peer-Reviewed Original ResearchGlycan structuresMass spectrometryPost-translational additionIntact glycopeptide analysisSite of modificationProtein glycosylationProtein modificationBioinformatics platformBiological processesGlycopeptide analysisMS fragmentationGlycoproteomic methodsGlycoproteomicsGlycosylationProtein isolationProteolytic digestionPeptide sequencesSystem-wide contextStudy of glycopeptidesPrimersRecent advancesExciting fieldProteinGlycansSpectrometryRevealing the human mucinome
Malaker SA, Riley NM, Shon DJ, Pedram K, Krishnan V, Dorigo O, Bertozzi CR. Revealing the human mucinome. Nature Communications 2022, 13: 3542. PMID: 35725833, PMCID: PMC9209528, DOI: 10.1038/s41467-022-31062-4.Peer-Reviewed Original ResearchConceptsModular protein domainsKey molecular signaturesProtein domainsTransmembrane proteinDetection of hundredsMucin domainGlycoprotein identificationHuman diseasesMolecular signaturesCell lysatesEnrichment strategyGlycoproteinVivo sourceOverlapping populationsImportant roleDomainStcEProteinLysatesOvarian cancer patientsComplex samples