2020
Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly
Sundaram R, Jin H, Li F, Shu T, Coleman J, Yang J, Pincet F, Zhang Y, Rothman JE, Krishnakumar SS. Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly. FEBS Letters 2020, 595: 297-309. PMID: 33222163, PMCID: PMC8068094, DOI: 10.1002/1873-3468.14006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCloning, MolecularEscherichia coliGene ExpressionGenetic VectorsLipid BilayersLiposomesMiceModels, MolecularNerve Tissue ProteinsOptical TweezersPhosphatidylcholinesPhosphatidylethanolaminesPhosphatidylserinesPolyethylene GlycolsProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant Fusion ProteinsSynaptosomal-Associated Protein 25Syntaxin 1Vesicle-Associated Membrane Protein 2ConceptsSNARE complex assemblyComplex assemblyMunc13-1 MUN domainDetailed structure-function analysisSNARE protein VAMP2Syntaxin 1/Structure-function analysisSynaptic vesicle fusionOptical tweezers studiesSNARE assemblySNARE motifMUN domainMunc18-1Syntaxin-1Munc13-1FRET spectroscopyLinker regionVesicle fusionDirect bindingPhospholipid bilayersPresynaptic membraneSNAP25AssemblyBindingRecruitsSynergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
Ramakrishnan S, Bera M, Coleman J, Rothman JE, Krishnakumar SS. Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis. ELife 2020, 9: e54506. PMID: 32401194, PMCID: PMC7220375, DOI: 10.7554/elife.54506.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsCalciumCalcium SignalingExocytosisHumansKineticsLiposomesMembrane FusionMiceMutationNerve Tissue ProteinsRatsSNARE ProteinsSynaptic VesiclesSynaptotagmin IVesicle-Associated Membrane Protein 2ConceptsSynaptotagmin-1Vesicular fusion machinerySingle-vesicle fusionFusion of vesiclesSNARE complexFusion machineryNeuronal exocytosisOligomer bindsRegulatory proteinsVesicle fusionSNAREpinsSynchronous fusionSynaptic vesiclesNovel mechanismVesiclesComplexinKinetic delayPrimary interfaceSynergistic roleFusionExocytosisMachineryProteinBindsMechanism
2018
Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis
Bello OD, Jouannot O, Chaudhuri A, Stroeva E, Coleman J, Volynski KE, Rothman JE, Krishnakumar SS. Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e7624-e7631. PMID: 30038018, PMCID: PMC6094142, DOI: 10.1073/pnas.1808792115.Peer-Reviewed Original ResearchConceptsRegulated exocytosisFusion machineryC2 domain proteinsCore fusion machinerySingle vesicle exocytosisConstitutive exocytosisPrincipal CaVesicular releaseMolecular mechanismsSensitive oligomersExocytosisPheochromocytoma cellsSelective disruptionSpontaneous fusionCritical roleMachineryOligomerizationDirect activationCentral componentStructural featuresConsiderable insightCalcium controlPHluorinSyt1SYT
2015
Re-visiting the trans insertion model for complexin clamping
Krishnakumar SS, Li F, Coleman J, Schauder CM, Kümmel D, Pincet F, Rothman JE, Reinisch KM. Re-visiting the trans insertion model for complexin clamping. ELife 2015, 4: e04463. PMID: 25831964, PMCID: PMC4384536, DOI: 10.7554/elife.04463.Peer-Reviewed Original ResearchAdaptor Proteins, Vesicular TransportAlgorithmsAnimalsCalorimetryCircular DichroismEntropyFluorescence Resonance Energy TransferHumansKineticsMembrane FusionModels, NeurologicalMutationNerve Tissue ProteinsNeuronsProtein BindingSignal TransductionSNARE ProteinsSynaptic TransmissionSynaptotagminsVesicle-Associated Membrane Protein 2
2014
Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins
Zorman S, Rebane AA, Ma L, Yang G, Molski MA, Coleman J, Pincet F, Rothman JE, Zhang Y. Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins. ELife 2014, 3: e03348. PMID: 25180101, PMCID: PMC4166003, DOI: 10.7554/elife.03348.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsEnergy TransferHumansKineticsModels, MolecularMolecular Sequence DataMultiprotein ComplexesOptical TweezersProtein FoldingProtein Structure, QuaternaryProtein Structure, SecondaryQa-SNARE ProteinsRatsSequence Homology, Amino AcidSNARE ProteinsThermodynamicsVesicle-Associated Membrane Protein 2Vesicular Transport ProteinsConceptsSoluble N-ethylmaleimide-sensitive factor attachment protein receptorsSNARE complexN-ethylmaleimide-sensitive factor attachment protein receptorsMembrane fusionFactor attachment protein receptorsAttachment protein receptorsHigh-resolution optical tweezersNeuronal SNARE complexFolding/assemblyEnergy releaseSNARE proteinsSingle-molecule levelProtein receptorsDomain associationOptical tweezersTerminal partZippering mechanismFusion kineticsZipperingComplexesAssemblyDifferent energeticsEnergyYeastTweezers
2011
A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion
Krishnakumar SS, Radoff DT, Kümmel D, Giraudo CG, Li F, Khandan L, Baguley SW, Coleman J, Reinisch KM, Pincet F, Rothman JE. A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. Nature Structural & Molecular Biology 2011, 18: 934-940. PMID: 21785412, PMCID: PMC3668341, DOI: 10.1038/nsmb.2103.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAmino Acid SequenceAnimalsBinding SitesCrystallography, X-RayHumansMembrane FusionModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsProtein Structure, TertiaryRatsSynaptosomal-Associated Protein 25SynaptotagminsSyntaxin 1Vesicle-Associated Membrane Protein 2