2024
The BICD2 dynein cargo adaptor binds to the HPV16 L2 capsid protein and promotes HPV infection
Speckhart K, Choi J, DiMaio D, Tsai B. The BICD2 dynein cargo adaptor binds to the HPV16 L2 capsid protein and promotes HPV infection. PLOS Pathogens 2024, 20: e1012289. PMID: 38829892, PMCID: PMC11230635, DOI: 10.1371/journal.ppat.1012289.Peer-Reviewed Original ResearchTrans Golgi networkL2 capsid proteinPromote infectionCapsid proteinIn vitro binding studiesDynein adaptorsGolgi networkCargo adaptorsBICD2 functionDynein motorsC-terminusDyneinSupport infectionMolecular basisBICD2EndosomesAdaptorProteinBinding studiesCell-basedVirusShort segmentHuman papillomavirusGolgiInfectionDe novo-designed transmembrane proteins bind and regulate a cytokine receptor
Mravic M, He L, Kratochvil H, Hu H, Nick S, Bai W, Edwards A, Jo H, Wu Y, DiMaio D, DeGrado W. De novo-designed transmembrane proteins bind and regulate a cytokine receptor. Nature Chemical Biology 2024, 20: 751-760. PMID: 38480980, PMCID: PMC11142920, DOI: 10.1038/s41589-024-01562-z.Peer-Reviewed Original ResearchTM proteinsTM regionTarget membrane proteinsComplex biological functionsTM domainTM helicesInteraction partnersTransmembrane proteinsMembrane proteinsReceptor homodimerizationBiological functionsCytokine receptorsBinding topologyAmino acidsProteinErythropoietin receptorHomodimerizationCell proliferationTransmembraneEpoRIn vitroMolecular modelingBinding modeReceptorsMotif
2023
Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry
Oh C, Buckley P, Choi J, Hierro A, DiMaio D. Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2307721120. PMID: 37819982, PMCID: PMC10589650, DOI: 10.1073/pnas.2307721120.Peer-Reviewed Original ResearchConceptsAmino acid sequenceAcid sequenceProtein segmentsVirus traffickingUnrelated cellular proteinsSequence-independent mannerIntracellular virus traffickingActivity of proteinsAmino acid segmentComplex biological functionsVirus entryTandem arraysProtein functionTrafficking factorsCellular proteinsEndosome membraneBiological functionsHPV16 pseudovirus infectionCellular factorsDiverse sequencesL2 capsid proteinsAllosteric inhibition of the T cell receptor by a designed membrane ligand
Ye Y, Morita S, Chang J, Buckley P, Wilhelm K, DiMaio D, Groves J, Barrera F. Allosteric inhibition of the T cell receptor by a designed membrane ligand. ELife 2023, 12: e82861. PMID: 37796108, PMCID: PMC10554751, DOI: 10.7554/elife.82861.Peer-Reviewed Original ResearchConceptsT cell receptorTCR activationCD3ζ subunitsTM ligandsComplex molecular machinesReceptor tyrosine kinase EphA2Cell receptorTM domainTransmembrane domainNative nanodiscsTCR subunitsAllosteric changesTM bundleCytoplasmic sideTM regionMolecular mechanismsExtracellular domainAllosteric inhibitionLck phosphorylationMolecular machinesMembrane receptorsAberrant activationSubunitsMembrane ligandsDecades of investigationNoncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry
Choi J, DiMaio D. Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. PLOS Pathogens 2023, 19: e1011648. PMID: 37703297, PMCID: PMC10519607, DOI: 10.1371/journal.ppat.1011648.Peer-Reviewed Original ResearchConceptsRetromer-mediated endosomeHPV entryGTP-bound formDominant negative Rab7Intracellular vesicular transportRetrograde transport pathwayVirus entryEndosomal exitRab GTPasesRab proteinsVesicle traffickingGolgi transportCellular proteinsVesicular transportProtein cargoKnockdown cellsIntracellular traffickingRab9AIncoming virusRab7EndosomesTraffickingTransport pathwaysProteinKey roleHPV is a cargo for the COPI sorting complex during virus entry
Harwood M, Woo T, Takeo Y, DiMaio D, Tsai B. HPV is a cargo for the COPI sorting complex during virus entry. Science Advances 2023, 9: eadc9830. PMID: 36662862, PMCID: PMC9858521, DOI: 10.1126/sciadv.adc9830.Peer-Reviewed Original ResearchConceptsCoat protein complex ITrans-Golgi networkProtein complex IGene knockdown strategyVirus entryCOPI complexProtein complexesCellular fractionationUnbiased proteomicsRetrograde traffickingCytoplasmic segmentGolgi stacksCellular cargoL2 mutantKnockdown strategyGolgi apparatusComplex IIncoming virusCell surfaceGolgiHost factorsCargoComplexesMutantsEndosomes
2022
Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection
Crite M, DiMaio D. Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection. Viruses 2022, 14: 804. PMID: 35458534, PMCID: PMC9027364, DOI: 10.3390/v14040804.Peer-Reviewed Original ResearchConceptsTM domainΓ-secretaseVirus traffickingCellular transmembrane proteinsNon-canonical rolePutative TM domainRetrograde transport pathwayΓ-secretase complexSubstrate proteinsMinor capsid protein L2Transmembrane proteinCatalytic subunitMutational studiesEndosomal membranesIntracellular traffickingProtein L2Cellular proteasesCellular factorsL2 capsid proteinsTM mutantsCapsid proteinHPV entryTraffickingL2 proteinProtein
2021
Retromer stabilizes transient membrane insertion of L2 capsid protein during retrograde entry of human papillomavirus
Xie J, Zhang P, Crite M, Lindsay CV, DiMaio D. Retromer stabilizes transient membrane insertion of L2 capsid protein during retrograde entry of human papillomavirus. Science Advances 2021, 7: eabh4276. PMID: 34193420, PMCID: PMC11057781, DOI: 10.1126/sciadv.abh4276.Peer-Reviewed Original ResearchCell-penetrating peptidesMembrane insertionL2 capsid proteinsArtificial transmembrane proteinsCapsid proteinComplex genetic interactionsTrafficking complexTrafficking stepsGenetic interactionsTraptamersTransmembrane proteinEndosome membraneRetrograde pathwayRetromerHPV entryIncoming virusProteinTransient insertionVirus entryCoherent pathwaysEntry routePathwaySequential passageDifferent stepsUbiquitination
2020
TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry
Xie J, Heim EN, Crite M, DiMaio D. TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry. Cell Reports 2020, 31: 107750. PMID: 32521275, PMCID: PMC7339955, DOI: 10.1016/j.celrep.2020.107750.Peer-Reviewed Original ResearchConceptsGTPase-activating proteinsRetrograde transport pathwayVirus entryRetromer activityHPV traffickingTrafficking complexMembrane recruitmentRetromer complexRab7-GTPCellular proteinsCellular compartmentsEndosome membraneRetromerRetrograde pathwayArtificial proteinsL2 capsid proteinsCapsid proteinRab7HPV entryTraffickingTBC1D5ProteinGTPTransport pathwaysPathwayCell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry
Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 6121-6128. PMID: 32123072, PMCID: PMC7084110, DOI: 10.1073/pnas.1917748117.Peer-Reviewed Original ResearchConceptsEssential protein-protein interactionsCellular protein complexesProtein-protein interactionsIntracellular virus traffickingRetrograde transport pathwaySites of replicationCell-penetrating sequenceProtein complexesCellular proteinsVirus replicationHPV16 pseudovirus infectionVirus traffickingL2 capsid proteinsAspects of infectionCapsid proteinHPV entryViral genomeViral proteinsIncoming virionsViral componentsHuman papillomavirus infectionProteinAntiviral targetDose-dependent blockVirus entry
2018
Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking
Zhang P, da Silva G, Deatherage C, Burd C, DiMaio D. Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking. Cell 2018, 174: 1465-1476.e13. PMID: 30122350, PMCID: PMC6128760, DOI: 10.1016/j.cell.2018.07.031.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCapsid ProteinsCell-Penetrating PeptidesEndosomesGolgi ApparatusGreen Fluorescent ProteinsHEK293 CellsHeLa CellsHuman papillomavirus 16HumansMutagenesisOncogene Proteins, ViralProtein TransportRecombinant Fusion ProteinsSequence AlignmentVirus AttachmentVirus InternalizationConceptsCell-penetrating peptidesTrans-Golgi networkNormal cell physiologyL2 proteinRetrograde transport pathwayShort protein segmentsHPV L2 proteinTrafficking factorsRetrograde traffickingCationic cell-penetrating peptidesCell physiologyEndosomal membranesProtein segmentsC-terminusBiological roleNon-enveloped virusesRetrograde pathwayL2 capsid proteinsMembrane passageCell penetrating peptideCapsid proteinViral proteinsProteinRetromerTransport pathwaysγ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection
Inoue T, Zhang P, Zhang W, Goodner-Bingham K, Dupzyk A, DiMaio D, Tsai B. γ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection. Journal Of Cell Biology 2018, 217: 3545-3559. PMID: 30006461, PMCID: PMC6168257, DOI: 10.1083/jcb.201804171.Peer-Reviewed Original Research
2017
Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions
He L, Steinocher H, Shelar A, Cohen EB, Heim EN, Kragelund BB, Grigoryan G, DiMaio D. Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions. ELife 2017, 6: e27701. PMID: 28869036, PMCID: PMC5597333, DOI: 10.7554/elife.27701.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsErythropoietin receptorTransmembrane proteinTransmembrane protein-protein interactionsTMD interactionsModel transmembrane proteinMouse erythropoietin receptorHuman erythropoietin receptorSingle methyl groupGrowth factor independenceSide chain methyl groupsCellular processesMouse cellsFactor independenceChain methyl groupsIntrinsic specificityToggle switchTraptamersMethyl groupProteinReceptor activitySpecific positionsReceptorsSpecificityOligomerizationTwo transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation
Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM, DiMaio D. Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7262-e7271. PMID: 28808001, PMCID: PMC5584431, DOI: 10.1073/pnas.1705622114.Peer-Reviewed Original ResearchConceptsTransmembrane domainE5 proteinE5 dimerPlatelet-derived growth factor β receptorGrowth factor β receptorActive dimeric conformationPDGF β-receptorTransmembrane dimerProtein bindsMembrane environmentReceptor dimerizationDimeric conformationAtom molecular dynamics simulationsBiochemical experimentsMouse cellsMolecular mechanismsActive dimerΒ receptorBovine papillomavirusProteinSpecific interactionsMembrane modelingReceptor activationDimerizationComplexes
2016
An Update on Canine, Feline and Bovine Papillomaviruses
da Costa R, Peleteiro M, Pires M, DiMaio D. An Update on Canine, Feline and Bovine Papillomaviruses. Transboundary And Emerging Diseases 2016, 64: 1371-1379. PMID: 27615361, DOI: 10.1111/tbed.12555.Peer-Reviewed Original ResearchConceptsAnimal healthSignificant economic lossesNumber of papillomavirusesCross-species infectionFarm animalsVeterinary practitionersNew viral typesEconomic lossesWild animalsWorldwide importanceFeline papillomavirusesAnimal papillomavirusesPrevalent pathogenDomestic catsPapillomavirus researchCell biologyFascinating modelAnimalsBovine papillomavirusRecent discoveryGreat impactPathogensFelineCanineWide range
2015
Biologically active LIL proteins built with minimal chemical diversity
Heim EN, Marston JL, Federman RS, Edwards AP, Karabadzhak AG, Petti LM, Engelman DM, DiMaio D. Biologically active LIL proteins built with minimal chemical diversity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e4717-e4725. PMID: 26261320, PMCID: PMC4553812, DOI: 10.1073/pnas.1514230112.Peer-Reviewed Original ResearchConceptsAmino acidsTransmembrane proteinSpecific biological activityPlatelet-derived growth factor β receptorArtificial transmembrane proteinsChemical diversityGrowth factor β receptorHydrophobic amino acidsLIL proteinsKnown proteinsIndividual amino acidsTransmembrane domainCellular contextDifferent amino acidsComplete mutagenesisMost proteinsBiological activityActive proteinSimple proteinSingle isoleucineSpecific sequencesProteinDiversityLeucineΒ receptorDirect Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection
Popa A, Zhang W, Harrison MS, Goodner K, Kazakov T, Goodwin EC, Lipovsky A, Burd CG, DiMaio D. Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection. PLOS Pathogens 2015, 11: e1004699. PMID: 25693203, PMCID: PMC4334968, DOI: 10.1371/journal.ppat.1004699.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkRetromer cargoTransmembrane proteinGolgi apparatusDirect bindingCoat protein complexCellular transmembrane proteinsVirus entryMinor capsid proteinCarboxy-terminal segmentProtein complexesL2 minor capsid proteinMinor capsid protein L2Early endosomesVesicular transportRetromerPlasma membraneEndosomal membranesBinding motifProtein L2Capsid proteinEndosomesL2 proteinViral componentsProtein
2014
Small transmembrane protein inhibitors of the platelet‐derived growth factor β receptor (LB215)
Petti L, Talbert‐Slagle K, Chacon K, Hochstrasser M, DiMaio D. Small transmembrane protein inhibitors of the platelet‐derived growth factor β receptor (LB215). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.lb215.Peer-Reviewed Original ResearchTransmembrane domainTransmembrane proteinPlatelet-derived growth factor β receptorProtein inhibitorGrowth factor receptor signalingSingle conservative amino acid substitutionSmall transmembrane proteinConservative amino acid substitutionsGrowth factor β receptorParticular tyrosine residueReceptor tyrosine kinasesAmino acid substitutionsSequence similarityGrowth factor receptorTraptamersReceptor dimerizationEffects of PDGFSmall proteinsTyrosine residuesExtracellular domainTyrosine kinaseAcid substitutionsReceptor signalingRetroviral libraryPDGFβR
2013
Public awareness of the HPV vaccine: A national population-based study.
Shrader A, Niccolai L, Mayne S, DiMaio D, Chagpar A. Public awareness of the HPV vaccine: A national population-based study. Journal Of Clinical Oncology 2013, 31: 1574-1574. DOI: 10.1200/jco.2013.31.15_suppl.1574.Peer-Reviewed Original ResearchHPV vaccineHuman papilloma virusNational population-based studyNational Health Interview SurveyPublic health educational programsHPV vaccine awarenessPopulation-based studyHealth Interview SurveyNumber of malignanciesHealth educational programsVaccine awarenessPapilloma virusNational guidelinesUS populationMultivariate analysisVaccineUninsured populationInterview SurveyMore womenSignificant predictorsWomenOlder counterpartsYounger cohortsMenPublic awarenessGenome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus
Lipovsky A, Popa A, Pimienta G, Wyler M, Bhan A, Kuruvilla L, Guie MA, Poffenberger AC, Nelson CD, Atwood WJ, DiMaio D. Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 7452-7457. PMID: 23569269, PMCID: PMC3645514, DOI: 10.1073/pnas.1302164110.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkHPV entryGenome-wide screenRetromer subunitsCellular genesScreen identifiesRetromerLate endosomesPotential antiviral targetsMultiple subunitsRetrograde pathwayTransport factorsCapsid proteinHeLa cellsCell entryAntiviral targetEndosomesGolgiVirus entryStable complexesEfficient infectionSubunitsHPV proteinsProteinImportant insights