2025
BRCA2 prevents PARPi-mediated PARP1 retention to protect RAD51 filaments
Lahiri S, Hamilton G, Moore G, Goehring L, Huang T, Jensen R, Rothenberg E. BRCA2 prevents PARPi-mediated PARP1 retention to protect RAD51 filaments. Nature 2025, 640: 1103-1111. PMID: 40140565, PMCID: PMC12161360, DOI: 10.1038/s41586-025-08749-x.Peer-Reviewed Original ResearchConceptsRad51 filamentsFormation of Rad51 filamentsTumor suppressor protein BRCA2Resected single-stranded DNAHomology-directed DNA repairBRCA2 mutationsDNA strand exchangeBRCA2-deficient tumorsBRCA2-deficient cellsDouble-stranded DNA breaksSingle-stranded DNAQuantitative single-molecule localization microscopySingle-molecule approachesStrand exchangeDNA substratesBRCA2 deficiencyCellular contextFilament stabilityDNA repairResponse to PARPiRAD51Sensitivity to PARPiDNA breaksBRCA2PARP1 inhibitionVimentin filament transport and organization revealed by single-particle tracking and 3D FIB-SEM
Renganathan B, Moore A, Yeo W, Petruncio A, Ackerman D, Weigel A, Team T, Pasolli H, Xu C, Shtengel G, Hess H, Serpinskaya A, Zhang H, Lippincott-Schwartz J, Gelfand V. Vimentin filament transport and organization revealed by single-particle tracking and 3D FIB-SEM. Journal Of Cell Biology 2025, 224: e202406054. PMID: 40062969, PMCID: PMC11893169, DOI: 10.1083/jcb.202406054.Peer-Reviewed Original ResearchSingle-molecule two- and three-colour FRET studies reveal a transition state in SNARE disassembly by NSF
Cheppali S, Li C, Xing W, Sun R, Yang M, Xue Y, Lu S, Yao J, Sun S, Chen C, Sui S. Single-molecule two- and three-colour FRET studies reveal a transition state in SNARE disassembly by NSF. Nature Communications 2025, 16: 250. PMID: 39747074, PMCID: PMC11695992, DOI: 10.1038/s41467-024-55531-0.Peer-Reviewed Original ResearchConceptsN-ethylmaleimide sensitive factorSNARE complexDisassembly of SNARE complexesStable four-helix bundleFour-helix bundleSNARE motifFluorescence spectroscopy approachesMinimal machineryAAA+ ATPasesProtein machineryAdapter proteinVesicle fusionMembrane fusionSyntaxinPhysiological processesSNAREProteinN-ethylmaleimideDisassemblySequential disassemblyMachinerySequential pathwayPathwayEukaryotesFusion
2024
Quantitative single-molecule analysis of assembly and Ca2+-dependent disassembly of synaptotagmin oligomers on lipid bilayers
Li F, Coleman J, Redondo-Morata L, Kalyana Sundaram R, Stroeva E, Rothman J, Pincet F. Quantitative single-molecule analysis of assembly and Ca2+-dependent disassembly of synaptotagmin oligomers on lipid bilayers. Communications Biology 2024, 7: 1608. PMID: 39627539, PMCID: PMC11615320, DOI: 10.1038/s42003-024-07317-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumLipid BilayersProtein MultimerizationSingle Molecule ImagingSynaptotagmin IConceptsSyt-1Lipid bilayerRing-like oligomersCa2+-evoked releaseSynaptotagmin-1Single-molecule imaging methodsSynaptic vesiclesBiochemical evidencePhysiological requirementsOligomerizationAnalysis of assembliesBilayerOligomersCa2+LipidAssemblyCa2Classes of oligomersMutationsVesiclesDisassemblyEvoked releaseA spatial expression atlas of the adult human proximal small intestine
Harnik Y, Yakubovsky O, Hoefflin R, Novoselsky R, Bahar Halpern K, Barkai T, Korem Kohanim Y, Egozi A, Golani O, Addadi Y, Kedmi M, Keidar Haran T, Levin Y, Savidor A, Keren-Shaul H, Mayer C, Pencovich N, Pery R, Shouval D, Tirosh I, Nachmany I, Itzkovitz S. A spatial expression atlas of the adult human proximal small intestine. Nature 2024, 632: 1101-1109. PMID: 39112711, DOI: 10.1038/s41586-024-07793-3.Peer-Reviewed Original ResearchConceptsExpression atlasSingle-molecule fluorescence in situ hybridizationLipid droplet assemblyAdult human gutFluorescence in situ hybridizationHuman proximal small intestineHuman small intestineHuman gutSpatial proteomicsProximal small intestineTip cellsGene expressionSmall intestineIron uptakeSpatial transcriptomicsVillus tip cellsImmune cell typesMouse small intestineCell typesDroplet assemblyImmunosuppressive rolePro-immunogenicAdult human small intestineT cellsZonated expression
2023
In situ structure of the red algal phycobilisome–PSII–PSI–LHC megacomplex
You X, Zhang X, Cheng J, Xiao Y, Ma J, Sun S, Zhang X, Wang H, Sui S. In situ structure of the red algal phycobilisome–PSII–PSI–LHC megacomplex. Nature 2023, 616: 199-206. PMID: 36922595, DOI: 10.1038/s41586-023-05831-0.Peer-Reviewed Original ResearchConceptsPhotosystem IOxygenic photosynthetic organismsSolid structural basisSitu structureLight-harvesting complexRed alga Porphyridium purpureumPhotosynthetic organismsIncomplete proteinStructural basisPhycobilisomesExcitation energy transfer pathwaysMegacomplexesPorphyridium purpureumPSIIPhotosystemsElectron tomographyLight energyAtomic resolutionStructural informationInteraction detailsAssemblyTransfer pathwayEnergy transfer pathwaysUnclear owingOrganismsAn integrated platform for high-throughput nanoscopy
Barentine A, Lin Y, Courvan E, Kidd P, Liu M, Balduf L, Phan T, Rivera-Molina F, Grace M, Marin Z, Lessard M, Rios Chen J, Wang S, Neugebauer K, Bewersdorf J, Baddeley D. An integrated platform for high-throughput nanoscopy. Nature Biotechnology 2023, 41: 1549-1556. PMID: 36914886, PMCID: PMC10497732, DOI: 10.1038/s41587-023-01702-1.Peer-Reviewed Original ResearchConceptsLarge data volumesUser-defined extensionsPlugin frameworkData compressionData volumeCamera frameFrame rateAnalysis platformAcquisition taskPlatformIntegrated acquisitionThroughputSingle-molecule localization microscopyTypical throughputHundreds of cellsThree-dimensional fluorescenceFrameworkTens of cellsLocalization microscopyWorkflow
2021
Live and fixed imaging of translation sites at single mRNA resolution in the Drosophila embryo
Vinter D, Hoppe C, Ashe H. Live and fixed imaging of translation sites at single mRNA resolution in the Drosophila embryo. STAR Protocols 2021, 2: 100812. PMID: 34585149, PMCID: PMC8450298, DOI: 10.1016/j.xpro.2021.100812.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrosophilaEmbryo, NonmammalianFemaleIn Situ Hybridization, FluorescenceMaleProtein BiosynthesisRNA, MessengerSingle Molecule ImagingSingle-Chain AntibodiesCovariance distributions in single particle tracking
Bailey MLP, Yan H, Surovtsev I, Williams JF, King MC, Mochrie SGJ. Covariance distributions in single particle tracking. Physical Review E 2021, 103: 032405. PMID: 33862686, PMCID: PMC9115892, DOI: 10.1103/physreve.103.032405.Peer-Reviewed Original ResearchConceptsCovariance distributionLocalization noiseMultivariate Gaussian random variablesGaussian random variablesSkew-normal distributionStatistical propertiesDisplacement covarianceRandom variablesThird central momentHeterogeneous noiseAnomalous diffusionProbability distributionTheory-experiment discrepancyViscoelastic polymer solutionsCentral momentsParticle trajectoriesTheoretical meansTheoretical equationsMotionSingle modeRecent experimentsTheoryNoiseParticle trackingCovariance
2020
Implementation of a 4Pi-SMS super-resolution microscope
Wang J, Allgeyer ES, Sirinakis G, Zhang Y, Hu K, Lessard MD, Li Y, Diekmann R, Phillips MA, Dobbie IM, Ries J, Booth MJ, Bewersdorf J. Implementation of a 4Pi-SMS super-resolution microscope. Nature Protocols 2020, 16: 677-727. PMID: 33328610, PMCID: PMC9118368, DOI: 10.1038/s41596-020-00428-7.Peer-Reviewed Original ResearchSequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination
Hirokawa S, Chure G, Belliveau NM, Lovely GA, Anaya M, Schatz DG, Baltimore D, Phillips R. Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination. Nucleic Acids Research 2020, 48: gkaa418-. PMID: 32449932, PMCID: PMC7337519, DOI: 10.1093/nar/gkaa418.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA CleavageLymphocytesNucleic Acid ConformationProtein Sorting SignalsReceptors, AntigenSingle Molecule ImagingV(D)J RecombinationVertebratesFlexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation
Bhattacharyya M, Lee YK, Muratcioglu S, Qiu B, Nyayapati P, Schulman H, Groves JT, Kuriyan J. Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation. ELife 2020, 9: e53670. PMID: 32149607, PMCID: PMC7141811, DOI: 10.7554/elife.53670.Peer-Reviewed Original ResearchMeSH KeywordsCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2CalmodulinCatalytic DomainEnzyme ActivationHumansPhosphorylationProtein IsoformsSingle Molecule ImagingConceptsInhibitory autophosphorylationResidue linkerDependent protein kinase IISingle-molecule assaysMammalian cell expressionProtein kinase IICaMKII variantsShort linkerTransphosphorylation ratesKinase domainCaMKII holoenzymeKinase IIAutophosphorylationHoloenzymeFlexible linkerPrincipal isoformCalcium signalsRelative levelsIsoformsCaMKIIHuman CaCell expressionLinkerVariantsSequence
2019
Chapter Eight Illuminating the virus life cycle with single-molecule FRET imaging
Lu M, Ma X, Mothes W. Chapter Eight Illuminating the virus life cycle with single-molecule FRET imaging. Advances In Virus Research 2019, 105: 239-273. PMID: 31522706, PMCID: PMC7246055, DOI: 10.1016/bs.aivir.2019.07.004.Peer-Reviewed Original ResearchMeSH Keywordsenv Gene Products, Human Immunodeficiency VirusFluorescence Resonance Energy TransferHIV-1Protein ConformationSingle Molecule ImagingVirus InternalizationConceptsVirus life cycleMolecular mechanismsViral proteinsSingle-molecule FRETBiological moleculesPrecise molecular mechanismsFörster resonance energy transfer (FRET) imagingLife cycleConformational dynamicsReal-time imagingEnergetics of transitionsNovel antiviral therapiesStructural intermediatesConformational changesConformational statesNative stateSmFRETRelevant conditionsElegant experimental designsAsymmetric intermediatesIntermediatesViral fusionViral glycoproteinsStructural methodsIntact virionsSynaptic vesicle fusion: today and beyond
Brose N, Brunger A, Cafiso D, Chapman ER, Diao J, Hughson FM, Jackson MB, Jahn R, Lindau M, Ma C, Rizo J, Shin YK, Söllner TH, Tamm L, Yoon TY, Zhang Y. Synaptic vesicle fusion: today and beyond. Nature Structural & Molecular Biology 2019, 26: 663-668. PMID: 31384060, DOI: 10.1038/s41594-019-0277-z.Peer-Reviewed Original ResearchAnimalsCalciumCryoelectron MicroscopyEndocytosisExocytosisHumansMacromolecular SubstancesMembrane FusionMembrane LipidsMembrane ProteinsNerve Tissue ProteinsNeurophysiologyNeurotransmitter AgentsOptical TweezersProtein Interaction MappingSingle Molecule ImagingSNARE ProteinsSynaptic TransmissionSynaptic VesiclesActive cargo positioning in antiparallel transport networks
Richard M, Blanch-Mercader C, Ennomani H, Cao W, De La Cruz EM, Joanny JF, Jülicher F, Blanchoin L, Martin P. Active cargo positioning in antiparallel transport networks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 14835-14842. PMID: 31289230, PMCID: PMC6660773, DOI: 10.1073/pnas.1900416116.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsBiological TransportMotionMyosinsSingle Molecule ImagingStochastic ProcessesAssociating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET
Lu M, Ma X, Castillo-Menendez LR, Gorman J, Alsahafi N, Ermel U, Terry DS, Chambers M, Peng D, Zhang B, Zhou T, Reichard N, Wang K, Grover JR, Carman BP, Gardner MR, Nikić-Spiegel I, Sugawara A, Arthos J, Lemke EA, Smith AB, Farzan M, Abrams C, Munro JB, McDermott AB, Finzi A, Kwong PD, Blanchard SC, Sodroski JG, Mothes W. Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Nature 2019, 568: 415-419. PMID: 30971821, PMCID: PMC6655592, DOI: 10.1038/s41586-019-1101-y.Peer-Reviewed Original ResearchConceptsSingle-molecule fluorescence resonance energy transferCryo-electron microscopy studiesHigh-resolution structuresFluorescence resonance energy transferState 1 conformationProline substitutionConformational statesResonance energy transferDisulfide bondsCell entryIntermediate conformationsReceptor moleculesGlycoprotein structureStructural studiesIntact virionsViral EnvCD4 receptor moleculeIntact virusConformationState 2TrimerState 1High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload
Satoh M, Nomura S, Harada M, Yamaguchi T, Ko T, Sumida T, Toko H, Naito AT, Takeda N, Tobita T, Fujita T, Ito M, Fujita K, Ishizuka M, Kariya T, Akazawa H, Kobayashi Y, Morita H, Takimoto E, Aburatani H, Komuro I. High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload. Journal Of Molecular And Cellular Cardiology 2019, 128: 77-89. PMID: 30611794, DOI: 10.1016/j.yjmcc.2018.12.018.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionHemodynamic overloadCardiomyocyte sizeExpression levelsGene expressionHeart failure stageSingle-cell RNA sequencingSingle-molecule RNAMyosin heavy chain βSingle-cell quantitative PCRFetal gene expressionFetal gene programSingle-cell analysis methodsSingle-molecule fluorescenceHeart failureSingle-cell levelPressure overloadAortic constrictionHypertrophy stageCardiac hypertrophyIsolated cardiomyocytesMyh7 expressionTemporal regulationRNA sequencingFetal genes
2018
Ligand Modulates Cross-Coupling between Riboswitch Folding and Transcriptional Pausing
Widom J, Nedialkov Y, Rai V, Hayes R, Brooks C, Artsimovitch I, Walter N. Ligand Modulates Cross-Coupling between Riboswitch Folding and Transcriptional Pausing. Molecular Cell 2018, 72: 541-552.e6. PMID: 30388413, PMCID: PMC6565381, DOI: 10.1016/j.molcel.2018.08.046.Peer-Reviewed Original ResearchMeSH KeywordsAptamers, NucleotideDNA-Directed RNA PolymerasesEscherichia coliEscherichia coli ProteinsFluorescence Resonance Energy TransferGene Expression Regulation, BacterialLigandsNucleic Acid ConformationNucleoside QProtein FoldingRiboswitchRNA FoldingRNA, BacterialSingle Molecule ImagingTranscription, GeneticConceptsCellular RNA transcriptsBacterial gene expressionRNA polymerase pausingCo-transcriptional foldingTranscriptional pausingTranscription machineryNascent RNAPolymerase pausingRiboswitch foldingRiboswitchRNA transcriptsGene expressionNative foldPhysiological cuesRNAPFunctional contextPausingFoldingNumerous classesAntibacterial drugsPreQTranscriptsRNAMachineryPseudoknotsSingle-Molecule Optical Tweezers Study of Regulated SNARE Assembly
Ma L, Jiao J, Zhang Y. Single-Molecule Optical Tweezers Study of Regulated SNARE Assembly. Methods In Molecular Biology 2018, 1860: 95-114. PMID: 30317500, PMCID: PMC6441361, DOI: 10.1007/978-1-4939-8760-3_6.Peer-Reviewed Original ResearchConceptsSoluble N-ethylmaleimide-sensitive factor attachment protein receptorsSNARE assemblyHigh-resolution optical tweezersN-ethylmaleimide-sensitive factor attachment protein receptorsMembrane fusionFactor attachment protein receptorsOptical tweezers studiesNeuronal SNARE assemblyIntracellular membrane fusionAttachment protein receptorsOptical tweezersΑ-SNAPDetailed experimental protocolCellular compartmentsRegulatory proteinsProtein receptorsDifferent cellsSpatiotemporal resolutionProteinAssemblyFusion processManipulation approachTweezersExperimental approachFusion
2017
Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images
Baddeley D, Bewersdorf J. Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images. Annual Review Of Biochemistry 2017, 87: 1-25. PMID: 29272143, DOI: 10.1146/annurev-biochem-060815-014801.Peer-Reviewed Original Research
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