2022
Molecular determinants of complexin clamping and activation function
Bera M, Ramakrishnan S, Coleman J, Krishnakumar SS, Rothman JE. Molecular determinants of complexin clamping and activation function. ELife 2022, 11: e71938. PMID: 35442188, PMCID: PMC9020821, DOI: 10.7554/elife.71938.Peer-Reviewed Original ResearchConceptsSynaptotagmin-1Single-vesicle fusionAccessory helixFusion clampHelical domainMolecular detailsComplexinMutational analysisVesicle releaseFusion kineticsMolecular determinantsSpecific interactionsInhibitory functionProbability of fusionRapid CaSNAREpinsAssembly processFusionClamping functionDomainHelixVesiclesFunctionMembraneInteraction
2020
Synergistic 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 ResearchConceptsSynaptotagmin-1Vesicular fusion machinerySingle-vesicle fusionFusion of vesiclesSNARE complexFusion machineryNeuronal exocytosisOligomer bindsRegulatory proteinsVesicle fusionSNAREpinsSynchronous fusionSynaptic vesiclesNovel mechanismVesiclesComplexinKinetic delayPrimary interfaceSynergistic roleFusionExocytosisMachineryProteinBindsMechanismSynaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
Tagliatti E, Bello OD, Mendonça PRF, Kotzadimitriou D, Nicholson E, Coleman J, Timofeeva Y, Rothman JE, Krishnakumar SS, Volynski KE. Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 3819-3827. PMID: 32015138, PMCID: PMC7035618, DOI: 10.1073/pnas.1920403117.Peer-Reviewed Original Research
2019
Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin
Grushin K, Wang J, Coleman J, Rothman JE, Sindelar CV, Krishnakumar SS. Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin. Nature Communications 2019, 10: 2413. PMID: 31160571, PMCID: PMC6546687, DOI: 10.1038/s41467-019-10391-x.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureActivation of SNAREsDependent membrane interactionsAnionic lipid headgroupsFusion clampActivator functionSNARE bundleSNARE proteinsMicroscopy structureC2B domainStructural basisSynaptotagmin-1SNAREpinsAliphatic loopsMembrane interactionsComplete assemblyLipid headgroupsLipid membranesNeurotransmitter releaseMembraneKey determinantSynaptotagminSyt1Calcium influxPartial insertion
2018
Rearrangements under confinement lead to increased binding energy of Synaptotagmin‐1 with anionic membranes in Mg2+ and Ca2+
Gruget C, Coleman J, Bello O, Krishnakumar SS, Perez E, Rothman JE, Pincet F, Donaldson SH. Rearrangements under confinement lead to increased binding energy of Synaptotagmin‐1 with anionic membranes in Mg2+ and Ca2+. FEBS Letters 2018, 592: 1497-1506. PMID: 29578584, DOI: 10.1002/1873-3468.13040.Peer-Reviewed Original ResearchStructural Insight into the Interaction of Synaptotagmin-1 and Snare Complex on Lipid Bilayer by Cryo-Electron Microscopy
Grushin K, Wang J, Coleman J, Rothman J, Sindelar C, Krishnakumar S. Structural Insight into the Interaction of Synaptotagmin-1 and Snare Complex on Lipid Bilayer by Cryo-Electron Microscopy. Biophysical Journal 2018, 114: 282a. DOI: 10.1016/j.bpj.2017.11.1622.Peer-Reviewed Original Research
2016
Ring-like oligomers of Synaptotagmins and related C2 domain proteins
Zanetti MN, Bello OD, Wang J, Coleman J, Cai Y, Sindelar CV, Rothman JE, Krishnakumar SS. Ring-like oligomers of Synaptotagmins and related C2 domain proteins. ELife 2016, 5: e17262. PMID: 27434670, PMCID: PMC4977156, DOI: 10.7554/elife.17262.Peer-Reviewed Original Research
2014
Calcium sensitive ring-like oligomers formed by synaptotagmin
Wang J, Bello O, Auclair SM, Wang J, Coleman J, Pincet F, Krishnakumar SS, Sindelar CV, Rothman JE. Calcium sensitive ring-like oligomers formed by synaptotagmin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 13966-13971. PMID: 25201968, PMCID: PMC4183308, DOI: 10.1073/pnas.1415849111.Peer-Reviewed Original ResearchConceptsSynaptic vesicle protein Synaptotagmin 1Cytosolic domainSoluble N-ethylmaleimide-sensitive factorN-ethylmaleimide-sensitive factorMembrane fusion machineryReceptor complex assemblyRing-like oligomersFusion machineryC2 domainComplex assemblySynaptotagmin-1Helical reconstructionFusion proceedsNovel mechanismStructural mechanismsLipid monolayersNeurotransmitter releaseAbsence of calciumPhysiological concentrationsRing formationPresence of calciumFree calcium ionsSynaptotagminCalcium influxCircular arrangement