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 cellsCheckpointGlycans
2021
Phosphatidylserine binding directly regulates TIM-3 function
Smith CM, Li A, Krishnamurthy N, Lemmon MA. Phosphatidylserine binding directly regulates TIM-3 function. Biochemical Journal 2021, 478: 3331-3349. PMID: 34435619, PMCID: PMC8454703, DOI: 10.1042/bcj20210425.Peer-Reviewed Original ResearchConceptsTim-3T cell receptorTherapeutic targetCo-signaling receptorsTim-3 functionTim-3 ligandTim-3 signalingCo-inhibitory receptorsCo-stimulatory receptorsImmune modulation approachesIL-2 secretionPotential therapeutic targetNF-κB signalingImportant therapeutic targetPD-1Jurkat cellsCultured Jurkat cellsT cellsCell receptorTCR stimulationReceptorsImportance of phosphatidylserineDifferent studiesCellsSignaling
2020
210 Regulation of TIM-3 by phosphatidylserine
Smith C, Li A, Krishnamurthy N, Lemmon M. 210 Regulation of TIM-3 by phosphatidylserine. Journal For ImmunoTherapy Of Cancer 2020, 8: a229-a229. DOI: 10.1136/jitc-2020-sitc2020.0210.Peer-Reviewed Original ResearchTim-3-expressing cellsTim-3 antibodyTim-3 functionTim-3Exhausted T cellsT cell signalingPD-1Receptor expressionT cellsTIM-1Tumor antigen-specific CD8Role of PST cell exhaustion phenotypeTim-3 receptorAntigen-specific CD8PD-1-mediated inhibitionPD-1 expressionImmune checkpoint blockadeMajority of patientsCheckpoint blockade therapyT cell dysfunctionImmune checkpoint receptorsAcute myelogenous leukemiaApoptotic cellsNew therapeutic targets