2024
Using in vivo intact structure for system-wide quantitative analysis of changes in proteins
Son A, Kim H, Diedrich J, Bamberger C, McClatchy D, Lipton S, Yates J. Using in vivo intact structure for system-wide quantitative analysis of changes in proteins. Nature Communications 2024, 15: 9310. PMID: 39468068, PMCID: PMC11519357, DOI: 10.1038/s41467-024-53582-x.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProtein footprinting methodGlobal expression profilingIn vivo conformationStructural alterations of proteinsCo-expressed proteinsMass spectrometry-based methodsAlterations of proteinsProteostasis dysfunctionSpectrometry-based methodsProtein misfoldingConformation of proteinsStructural changesLysine residuesDynamic structural changesBiological functionsProteomics experimentsDimethyl labelingExpression profilesProtein conformationConformational changesProteinIntact proteinDesign of therapeutic interventionsMeasuring dynamic structural changesPre‐diagnostic plasma advanced glycation end‐products and soluble receptor for advanced glycation end‐products and mortality in colorectal cancer patients
Li J, Baker J, Aglago E, Zhao Z, Jiao L, Freisling H, Hughes D, Eriksen A, Tjønneland A, Severi G, Katzke V, Kaaks R, Schulze M, Masala G, Pala V, Pasanisi F, Tumino R, Padroni L, Vermeulen R, Gram I, Braaten T, Jakszyn P, Sánchez M, Gómez‐Gómez J, Moreno‐Iribas C, Amiano P, Papier K, Weiderpass E, Huybrechts I, Heath A, Schalkwijk C, Jenab M, Fedirko V. Pre‐diagnostic plasma advanced glycation end‐products and soluble receptor for advanced glycation end‐products and mortality in colorectal cancer patients. International Journal Of Cancer 2024, 155: 1982-1995. PMID: 39057841, DOI: 10.1002/ijc.35114.Peer-Reviewed Original ResearchConceptsAssociated with CRC-specificAdvanced glycation end productsPlasma advanced glycation end productsColorectal cancerCRC-specificOverall mortalityGlycation end productsSoluble receptorCancer patientsIntracellular signaling alterationsMultivariable-adjusted Cox proportional hazards regressionCancer and NutritionCox proportional hazards regressionEuropean Prospective InvestigationFollow-up periodColorectal cancer casesColorectal cancer patientsProportional hazards regressionUltra-performance liquid chromatography mass spectrometryColorectal cancer diagnosisEnzyme-linked immunosorbent assayColorectal cancer survivalProspective InvestigationChronic inflammationSRAGETwo DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids
Frisbie V, Hashimoto H, Xie Y, De Luna Vitorino F, Baeza J, Nguyen T, Yuan Z, Kiselar J, Garcia B, Debler E. Two DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids. Nature Communications 2024, 15: 2467. PMID: 38503750, PMCID: PMC10951340, DOI: 10.1038/s41467-024-46637-6.Peer-Reviewed Original ResearchConceptsMotif VIDot1 enzymesMechanism of substrate recognitionH2B mono-ubiquitinationHistone H3 lysine 79Active-site loopH3 lysine 79Histone H3 lysineEnzyme-substrate complexMotif IVTri-methyltransferaseSubstrate recognitionMethylation kineticsMono-ubiquitinationLysine 79Substrate preferenceH3 lysineTri-methylationDOT1BAcid residuesDot1Ala residuesKinetoplastidsMotifBiochemical analysis
2023
Lysine Demethylation in Pathogenesis
Cao J, Yan Q. Lysine Demethylation in Pathogenesis. Advances In Experimental Medicine And Biology 2023, 1433: 1-14. PMID: 37751133, DOI: 10.1007/978-3-031-38176-8_1.ChaptersConceptsLysine demethylasesLSD1/KDM1AHistone lysine methylationHistone lysine methyltransferasesMajor epigenetic mechanismsNormal developmentNon-histone substratesSpecific small molecule inhibitorsSmall molecule inhibitorsLysine methylationLysine methyltransferasesHistone methylationHistone lysineLysine demethylationEpigenetic mechanismsDNA repairArginine residuesHuman diseasesMore subfamiliesMolecule inhibitorsLysine modificationDemethylasesMethylationTreatment of cancerEnzymeKDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic
Zhang S, Cao J, Yan Q. KDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic. Advances In Experimental Medicine And Biology 2023, 1433: 113-137. PMID: 37751138, DOI: 10.1007/978-3-031-38176-8_6.ChaptersConceptsPlant homeodomainFamily proteinsKey epigenetic markCell fate determinationHistone methylation marksCancer type-dependent mannerKetoglutarate-dependent dioxygenasesSelective KDM5 inhibitorsTumor suppressive functionType-dependent mannerEpigenetic marksTumor suppressive roleFate determinationJumonji CLysine 4Active chromatinMethylation marksHistone H3Lysine demethylasesCatalytic coreKDM5 inhibitorsDrug targetsKDM5Cancer metastasisSuppressive roleAcetyl-methyllysine marks chromatin at active transcription start sites
Lu-Culligan W, Connor L, Xie Y, Ekundayo B, Rose B, Machyna M, Pintado-Urbanc A, Zimmer J, Vock I, Bhanu N, King M, Garcia B, Bleichert F, Simon M. Acetyl-methyllysine marks chromatin at active transcription start sites. Nature 2023, 622: 173-179. PMID: 37731000, PMCID: PMC10845139, DOI: 10.1038/s41586-023-06565-9.Peer-Reviewed Original ResearchConceptsPost-translational modificationsLysine residuesActive transcription start sitesTranscription start siteRange of speciesChromatin biologyChromatin proteinsLysine methylationActive chromatinProteins BRD2Transcriptional initiationLysine acetylationHistone H4Start siteMammalian tissuesHuman diseasesSame residuesMethylationAcetylationChromatinResiduesProteinBiological signalsHistonesBRD2Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1
Abini-Agbomson S, Gretarsson K, Shih R, Hsieh L, Lou T, De Ioannes P, Vasilyev N, Lee R, Wang M, Simon M, Armache J, Nudler E, Narlikar G, Liu S, Lu C, Armache K. Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1. Molecular Cell 2023, 83: 2872-2883.e7. PMID: 37595555, DOI: 10.1016/j.molcel.2023.07.020.Peer-Reviewed Original ResearchConceptsNon-catalytic activitiesNon-catalytic mechanismHistone H4 lysine 20Histone variant H2A.ZH4 lysine 20Large macromolecular complexesCatalytic activityHeterochromatin formationHeterochromatin functionVariant H2A.ZLysine 20Nucleosome substratesGenomic stabilityDNA replicationNucleosomal DNAHistone methyltransferaseChromatin condensationSUV420H1Histone octamerMacromolecular complexesCryoelectron microscopyCellular analysisEssential roleDistinct phenotypesCrucial role
2022
Ancestral archaea expanded the genetic code with pyrrolysine
Guo LT, Amikura K, Jiang HK, Mukai T, Fu X, Wang YS, O’Donoghue P, Söll D, Tharp JM. Ancestral archaea expanded the genetic code with pyrrolysine. Journal Of Biological Chemistry 2022, 298: 102521. PMID: 36152750, PMCID: PMC9630628, DOI: 10.1016/j.jbc.2022.102521.Peer-Reviewed Original ResearchConceptsAminoacylation efficiencyGenetic code expansionDomains of lifePyrrolysyl-tRNA synthetaseTRNA-binding domainFull-length enzymeNoncanonical amino acidsAmino acid substratesMolecular phylogenyDiverse archaeaCoevolutionary historyTRNA sequencesGenetic codeCode expansionDiscriminator basesMethanogenic archaeaMethanosarcina mazeiPylRSSubstrate spectrumTRNAArchaeaMultiple organismsLiving cellsAcid substratesAmino acidsTargeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy
Ueno D, Vasquez JC, Sule A, Liang J, van Doorn J, Sundaram R, Friedman S, Caliliw R, Ohtake S, Bao X, Li J, Ye H, Boyd K, Huang RR, Dodson J, Boutros P, Bindra RS, Shuch B. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy. Oncotarget 2022, 13: 1054-1067. PMID: 36128328, PMCID: PMC9477221, DOI: 10.18632/oncotarget.28273.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCarcinoma, Renal CellCitric Acid CycleDioxygenasesDNAFumarate HydrataseFumaratesHumansJumonji Domain-Containing Histone DemethylasesKidney NeoplasmsLysineMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSuccinate DehydrogenaseSuccinatesTemozolomideConceptsRenal cell carcinomaPoly ADP-ribose polymerase inhibitorsADP-ribose polymerase inhibitorsCell carcinomaSDH-deficient renal cell carcinomaPolymerase inhibitorsLow-dose temozolomideAggressive renal cell carcinomaHereditary cancer syndromesNovel therapeutic strategiesDeficient murine modelStandard dosingTMZ resultsMurine modelTherapeutic strategiesCombination treatmentCancer syndromesTumor growthHomologous recombination DNA repair pathwayAccumulation of fumarateHR deficiencyPARP inhibitionTemozolomideChemotherapyCarcinomaThe tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism
Zhang H, Gong X, Zhao Q, Mukai T, Vargas-Rodriguez O, Zhang H, Zhang Y, Wassel P, Amikura K, Maupin-Furlow J, Ren Y, Xu X, Wolf YI, Makarova KS, Koonin EV, Shen Y, Söll D, Fu X. The tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism. Nucleic Acids Research 2022, 50: gkac271-. PMID: 35466371, PMCID: PMC9071458, DOI: 10.1093/nar/gkac271.Peer-Reviewed Original ResearchConceptsGenetic code expansionCode expansionDistinct non-canonical amino acidsOrthogonal aminoacyl-tRNA synthetase/tRNA pairsAminoacyl-tRNA synthetase/tRNA pairsPyrrolysyl-tRNA synthetase/Halophilic archaeon Haloferax volcaniiAdditional coding capacityDistinct noncanonical amino acidsNon-canonical amino acidsArchaeon Haloferax volcaniiDiscriminator baseAmino acidsPyrrolysyl-tRNA synthetaseNoncanonical amino acidsSite-specific incorporationMotif 2 loopSingle base changeDistinct tRNAsTRNA pairsHaloferax volcaniiUAA codonGenetic codeDiscriminator basesTRNA structureThe histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication
Davarinejad H, Huang YC, Mermaz B, LeBlanc C, Poulet A, Thomson G, Joly V, Muñoz M, Arvanitis-Vigneault A, Valsakumar D, Villarino G, Ross A, Rotstein BH, Alarcon EI, Brunzelle JS, Voigt P, Dong J, Couture JF, Jacob Y. The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication. Science 2022, 375: 1281-1286. PMID: 35298257, PMCID: PMC9153895, DOI: 10.1126/science.abm5320.Peer-Reviewed Original ResearchConceptsTetratricopeptide repeat domainDNA polymerase thetaMulticellular eukaryotesHistone H3.1Replication forksChromatin maturationRepeat domainDNA repairGenomic instabilityPolymerase thetaPosition 31Amino acidsH3.1PlantsReplicationEukaryotesH3.3HistonesMonomethylationVariantsCommon strategyForkResiduesMaturationFunction
2021
H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation
Dong J, LeBlanc C, Poulet A, Mermaz B, Villarino G, Webb KM, Joly V, Mendez J, Voigt P, Jacob Y. H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation. The Plant Cell 2021, 33: 961-979. PMID: 33793815, PMCID: PMC8226292, DOI: 10.1093/plcell/koaa027.Peer-Reviewed Original ResearchConceptsGenome stabilityGenomic instabilityHistone acetylationSAGA-like complexesMultiple lysine residuesArabidopsis GCN5ARABIDOPSIS TRITHORAXArabidopsis thalianaTranscriptional silencingHeterochromatin defectsDouble mutantDNA replicationEpigenetic mechanismsGCN5Molecular roleEssential functionsDiverse rolesMolecular mechanismsLysine residuesProtein 5AcetylationMutantsPlantsADA2bATXR6
2020
Protein Lysine Acetylation An Unexpected Mediator in Pancreatitis
Gorelick FS. Protein Lysine Acetylation An Unexpected Mediator in Pancreatitis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 883-884. PMID: 33279460, PMCID: PMC7900832, DOI: 10.1016/j.jcmgh.2020.11.010.Peer-Reviewed Original ResearchEnhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma
Helmsauer K, Valieva M, Ali S, Chamorro González R, Schöpflin R, Röefzaad C, Bei Y, Dorado Garcia H, Rodriguez-Fos E, Puiggròs M, Kasack K, Haase K, Keskeny C, Chen C, Kuschel L, Euskirchen P, Heinrich V, Robson M, Rosswog C, Toedling J, Szymansky A, Hertwig F, Fischer M, Torrents D, Eggert A, Schulte J, Mundlos S, Henssen A, Koche R. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nature Communications 2020, 11: 5823. PMID: 33199677, PMCID: PMC7669906, DOI: 10.1038/s41467-020-19452-y.Peer-Reviewed Original ResearchConceptsExtrachromosomal circular DNACore regulatory circuitEnhancer hijackingAmplicon structureDistal chromosomal fragmentsGene regulatory elementsMYCN amplificationChIP-seqShort readsHi-C.ATAC-seqChromatin landscapeNanopore sequencingRegulatory elementsRegulatory circuitsChromosome fragmentsMYCN ampliconGene copiesProximal enhancerCo-amplifiedCircular DNAAmpliconsMYCN overexpressionFunctional relevanceMYCN
2019
H2A.Z facilitates licensing and activation of early replication origins
Long H, Zhang L, Lv M, Wen Z, Zhang W, Chen X, Zhang P, Li T, Chang L, Jin C, Wu G, Wang X, Yang F, Pei J, Chen P, Margueron R, Deng H, Zhu M, Li G. H2A.Z facilitates licensing and activation of early replication origins. Nature 2019, 577: 576-581. PMID: 31875854, DOI: 10.1038/s41586-019-1877-9.Peer-Reviewed Original ResearchConceptsOrigin recognition complexHistone variant H2A.ZEarly replication originsReplication originsVariant H2A.ZReplication timingChromatin-based regulatory mechanismsEarly replication timingGenome-wide studiesNascent DNA strandsH2A.Z resultsNucleosome bindsDNA replicationH2A.ZHistone H4Cell cycle1Precise duplicationRegulated processDNA sequencesRegulatory mechanismsHeLa cellsDNA strandsORC1Firing efficiencyGenomeBiocatalytic Reversal of Advanced Glycation End Product Modification
Kim NY, Goddard TN, Sohn S, Spiegel DA, Crawford J. Biocatalytic Reversal of Advanced Glycation End Product Modification. ChemBioChem 2019, 20: 2402-2410. PMID: 31013547, PMCID: PMC6768434, DOI: 10.1002/cbic.201900158.Peer-Reviewed Original ResearchConceptsImproved catalytic propertiesCondensation of sugarsLysine structureStructural homology analysisCatalytic propertiesSite-directed mutagenesisLead catalystFree amino acid formAcid formEnzyme variantsMaillard reactionHomology analysisCausal agentAuthentic ligandMolecular levelAdvanced glycation end product modificationAmino acid formMnmCLack of toolsAdvanced glycation end productsCatalystPeptidomimeticsLigandsVariantsMoleculesHistone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, Chen Z, Deng X, Xiao G, Auer F, Klemm L, Wu H, Zuo Z, Qin X, Dong Y, Zhou Y, Qin H, Tao S, Du J, Liu J, Lu Z, Yin H, Mesquita A, Yuan CL, Hu YC, Sun W, Su R, Dong L, Shen C, Li C, Qing Y, Jiang X, Wu X, Sun M, Guan JL, Qu L, Wei M, Müschen M, Huang G, He C, Yang J, Chen J. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally. Nature 2019, 567: 414-419. PMID: 30867593, PMCID: PMC6438714, DOI: 10.1038/s41586-019-1016-7.Peer-Reviewed Original ResearchConceptsM6A methyltransferase complexHistone H3 trimethylationH3 trimethylationHistone modificationsImportant post-transcriptional mechanismMouse embryonic stem cellsGene expression regulationRNA polymerase IIPrevalent internal modificationPost-transcriptional mechanismsEmbryonic stem cellsN6-methyladenosine (m<sup>6</sup>A) mRNA modificationM6A depositionTranscription elongationNascent RNAMethyltransferase complexPolymerase IIExpression regulationGene expression1RNA methylationMRNA modificationMETTL14 knockdownH3K36me3M6A modificationCell stemnessCrystallographic identification of spontaneous oxidation intermediates and products of protein sulfhydryl groups
Wang J. Crystallographic identification of spontaneous oxidation intermediates and products of protein sulfhydryl groups. Protein Science 2019, 28: 472-477. PMID: 30592103, PMCID: PMC6371210, DOI: 10.1002/pro.3568.Peer-Reviewed Original ResearchConceptsLys side chainsSide chainsO bridgesChemical identificationCrystal structureElectron density featuresCross-linking speciesCys side chainDirect chemical identificationProtein crystal structuresMass spectrometric analysisOxidation intermediatesCys-245Primary aminesMethylene groupCrystallographic identificationSpectrometric analysisDehydration mechanismLys-158Protein sulfhydryl groupsSulfhydryl groupsProtein structureChainCHCys residues
2018
Regulation of C-C chemokine receptor 5 (CCR5) stability by Lys197 and by transmembrane protein aptamers that target it for lysosomal degradation
Petti LM, Marlatt SA, Luo Y, Scheideman EH, Shelar A, DiMaio D. Regulation of C-C chemokine receptor 5 (CCR5) stability by Lys197 and by transmembrane protein aptamers that target it for lysosomal degradation. Journal Of Biological Chemistry 2018, 293: 8787-8801. PMID: 29678881, PMCID: PMC5995508, DOI: 10.1074/jbc.ra117.001067.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsC motif chemokine receptor 5Transmembrane helicesAmino acidsProtein aptamerFifth transmembrane helixUncharged amino acidsSpecific amino acidsProtein-coupled receptorsSubstitution of LysTraptamersReceptor stabilityLysosomal degradationHomologous positionsDiverse mechanismsChemokine receptor 5Initial characterizationNew therapeutic approachesHuman T cellsStable complexesCCR5 expressionCentral roleNew insightsChemokine receptorsHelixElevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141–147 in Taiwanese with Alzheimer's disease
Lin CY, Sheu JJ, Tsai IS, Wang ST, Yang LY, Hsu IU, Chang HW, Lee HM, Kao SH, Lee CK, Chen CH, Lin YF. Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141–147 in Taiwanese with Alzheimer's disease. Clinical Biochemistry 2018, 56: 75-82. PMID: 29680706, DOI: 10.1016/j.clinbiochem.2018.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAntibody SpecificityApolipoprotein A-IAutoantibodiesAutoimmunityBiomarkersCase-Control StudiesEnzyme-Linked Immunosorbent AssayFemaleGlycation End Products, AdvancedHumansImmunoglobulin MLysineMalePeptide FragmentsProtein Processing, Post-TranslationalPsychiatric Status Rating ScalesROC CurveTaiwanUp-RegulationConceptsAdvanced glycation end productsSpecific advanced glycation end productsAlzheimer's diseaseMini-Mental State Examination scoreMental State Examination scoreEarly AD markersEarly AD pathologyState Examination scoreEarly disease statesGlycation end productsRelated autoantibodiesAD markersIgM levelsAD pathologyElevated IgMAD seraAD patientsDisease progressionAD biomarkersApolipoprotein A1IgMAutoantibodiesApoA1Serum samplesWestern blotting
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