2024
Lipid scrambling is a general feature of protein insertases
Li D, Rocha-Roa C, Schilling M, Reinisch K, Vanni S. Lipid scrambling is a general feature of protein insertases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319476121. PMID: 38621120, PMCID: PMC11047089, DOI: 10.1073/pnas.2319476121.Peer-Reviewed Original ResearchConceptsIntegral membrane proteinsEndoplasmic reticulumMembrane proteinsPolypeptide chainLipid scramblingNascent polypeptide chainsVesicle traffickingBiochemical reconstitutionCytosolic leafletProtein insertionMembrane expansionInsertaseMembrane dynamicsHydrophilic grooveHydrophobic membrane interiorScramblaseProteinLipidMembraneBilayer leafletsMembrane interiorOrganellesReticulumPolypeptideTraffickingSpartin-mediated lipid transfer facilitates lipid droplet turnover
Wan N, Hong Z, Parson M, Korfhage J, Burke J, Melia T, Reinisch K. Spartin-mediated lipid transfer facilitates lipid droplet turnover. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314093121. PMID: 38190532, PMCID: PMC10801920, DOI: 10.1073/pnas.2314093121.Peer-Reviewed Original Research
2021
The Role of VPS13 and Related Proteins in lipid transport at membrane contact sites
Reinisch K. The Role of VPS13 and Related Proteins in lipid transport at membrane contact sites. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.00089.Peer-Reviewed Original Research
2016
Control of plasma membrane lipid homeostasis by the extended synaptotagmins
Saheki Y, Bian X, Schauder CM, Sawaki Y, Surma MA, Klose C, Pincet F, Reinisch KM, De Camilli P. Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nature Cell Biology 2016, 18: 504-515. PMID: 27065097, PMCID: PMC4848133, DOI: 10.1038/ncb3339.Peer-Reviewed Original ResearchConceptsSMP domainE-Syt1ER-PM tethersMembrane lipid homeostasisPlasma membrane lipidsEndoplasmic reticulum proteinAccumulation of diacylglycerolE-SytsExtended synaptotagminsMolecular basisMajor glycerolipidsReticulum proteinsMetabolic recyclingMembrane lipidsLipid homeostasisPLC activationSynaptotagminSustained accumulationHomeostatic responseDiacylglycerolGlycerolipidsMetabolic changesGenomeCa2Accumulation
2015
The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane
Baskin JM, Wu X, Christiano R, Oh MS, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM, De Camilli P. The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane. Nature Cell Biology 2015, 18: 132-138. PMID: 26571211, PMCID: PMC4689616, DOI: 10.1038/ncb3271.Peer-Reviewed Original ResearchThe Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs
Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Developmental Cell 2015, 34: 569-576. PMID: 26343456, PMCID: PMC4594837, DOI: 10.1016/j.devcel.2015.08.010.Peer-Reviewed Original ResearchConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPre-autophagosomal structureAtg8/LC3 proteinsPathogen Legionella pneumophilaHigh-curvature membranesMembrane transport pathwaysCytosol of cellsEffector proteinsCatalytic domainHost cytosolRavZAutophagy proteinsLC3 proteinPathogenic microbesSubstrate affinityProteinIntermediate membraneLegionella pneumophilaAutophagosomesAutophagyCytosolTransport pathwaysInterfacial activationMembraneRe-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
Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus
Cai Y, Deng Y, Horenkamp F, Reinisch KM, Burd CG. Sac1–Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. Journal Of Cell Biology 2014, 206: 485-491. PMID: 25113029, PMCID: PMC4137058, DOI: 10.1083/jcb.201404041.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCatalysisCrystallography, X-RayEndoplasmic ReticulumGolgi ApparatusGreen Fluorescent ProteinsMembrane ProteinsModels, MolecularMultiprotein ComplexesPhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesProtein BindingProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsGolgi apparatusHomology domainRegulation of phosphatidylinositolN-terminal subdomainN-terminal portionPhosphoinositide phosphataseFamily proteinsSignal terminationEndoplasmic reticulumPhosphatidylinositolMembrane compositionSAC1Dual functionPhosphoinositideEffectorsPhosphataseAmyotrophic lateral sclerosisCharcot-MarieBroad distributionVps74OrthologuesTooth disordersGOLPH3MannosyltransferaseLateral sclerosisStructure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer
Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR, De Camilli P, Reinisch KM. Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer. Nature 2014, 510: 552-555. PMID: 24847877, PMCID: PMC4135724, DOI: 10.1038/nature13269.Peer-Reviewed Original ResearchDiversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation
Langemeyer L, Bastos R, Cai Y, Itzen A, Reinisch KM, Barr FA. Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation. ELife 2014, 3: e01623. PMID: 24520163, PMCID: PMC3919270, DOI: 10.7554/elife.01623.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAspartic AcidBacterial ProteinsCatalytic DomainDeath Domain Receptor Signaling Adaptor ProteinsDNA-Binding ProteinsEnzyme ActivationGlutamineGuanine Nucleotide Exchange FactorsHeLa CellsHumansHydrolysisListeriaModels, MolecularMutagenesis, Site-DirectedMutationProtein ConformationRab GTP-Binding ProteinsRab1 GTP-Binding ProteinsRab5 GTP-Binding ProteinsSignal TransductionTransfectionConceptsActive site residuesGTP hydrolysis mechanismNucleotide-free formActive site glutamineSwitch II regionDifferent RabsRab activationRab GTPasesGTPase activationGlutamine mutantNucleotide exchangeGDP releaseRabActivation mechanismActivation pathwayActive formPathwayResiduesActivationII regionRAPlasticityGTPasesRab5GEF
2013
The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway
Tan D, Cai Y, Wang J, Zhang J, Menon S, Chou HT, Ferro-Novick S, Reinisch KM, Walz T. The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 19432-19437. PMID: 24218626, PMCID: PMC3845172, DOI: 10.1073/pnas.1316356110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyChlorocebus aethiopsChromatography, GelCloning, MolecularCOP-Coated VesiclesCOS CellsElectroporationEscherichia coliImage Processing, Computer-AssistedMicroscopy, ElectronMicroscopy, FluorescenceModels, MolecularProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsVesicular Transport ProteinsConceptsPhagophore assembly siteCOPII vesiclesAssembly sitesRab GTPase Ypt1Electron microscopy structureTargeting of ERTRAPPIII complexFusion machineryMicroscopy structureCOPII coatMacroautophagy pathwayExchange factorSubunit associatesMembrane sourceEM structuresAcceptor compartmentTRAPPIIITRAPPIVesiclesMacroautophagyTrs85COPIISec23Ypt1Mammals
2011
Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate
Wu X, Bradley MJ, Cai Y, Kümmel D, De La Cruz EM, Barr FA, Reinisch KM. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 18672-18677. PMID: 22065758, PMCID: PMC3219131, DOI: 10.1073/pnas.1110415108.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBiological TransportCrystallography, X-RayDeath Domain Receptor Signaling Adaptor ProteinsGuanineGuanine Nucleotide Exchange FactorsHumansKineticsNucleotidesProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryRab GTP-Binding ProteinsRab1 GTP-Binding ProteinsConceptsGuanine nucleotide exchange factorsDENN domain proteinsMembrane traffic pathwaysNucleotide exchange factorsGDP-bound formGTP-bound formSwitch regions IHigher eukaryotesRab GTPasesGEF familyEukaryotic cellsTraffic pathwaysExchange factorSwitch INucleotide bindingKey regulatorConformational changesFirst structureNovel insightsRab35ProteinDENND1BEukaryotesRegion IGTPasesA 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
2010
Structure and function of the polymerase core of TRAMP, a RNA surveillance complex
Hamill S, Wolin SL, Reinisch KM. Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 15045-15050. PMID: 20696927, PMCID: PMC2930566, DOI: 10.1073/pnas.1003505107.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceBase SequenceBinding SitesCrystallography, X-RayDNA-Directed DNA PolymeraseModels, MolecularMolecular Sequence DataMultiprotein ComplexesProtein Interaction Domains and MotifsRecombinant ProteinsRNA, FungalSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidStatic ElectricitySubstrate SpecificityConceptsZinc knuckle motifHigher eukaryotesSubstrate recognitionRNA polymeraseCentral domainInitial substrate recognitionRNA 3' endsTRAMP complexRNA surveillanceZinc knuckleCharacterized enzymesAberrant RNAsSurveillance complexPolymerase coreRNA bindingAir2pNucleotidyl transferaseTrf4pN-terminusEukaryotesInteraction surfacePolymeraseMotifNucleic acidsComplexesStructure of a C-terminal fragment of its Vps53 subunit suggests similarity of Golgi-associated retrograde protein (GARP) complex to a family of tethering complexes
Vasan N, Hutagalung A, Novick P, Reinisch KM. Structure of a C-terminal fragment of its Vps53 subunit suggests similarity of Golgi-associated retrograde protein (GARP) complex to a family of tethering complexes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14176-14181. PMID: 20660722, PMCID: PMC2922553, DOI: 10.1073/pnas.1009419107.Peer-Reviewed Original ResearchConceptsGolgi-associated retrograde proteinC-terminusC-terminal fragmentGolgi-associated retrograde protein (GARP) complexCommon evolutionary originAlpha-helical bundleTrans-Golgi networkEndosome-derived vesiclesMembrane trafficVesicle recognitionEvolutionary originProtein complexesOligomeric GolgiTerminusSubunitsProteinComplexesDsl1ExocystFragmentsEndosomesGolgiFamilyMutationsVesicles
2009
Insights into MHC Class I Peptide Loading from the Structure of the Tapasin-ERp57 Thiol Oxidoreductase Heterodimer
Dong G, Wearsch PA, Peaper DR, Cresswell P, Reinisch KM. Insights into MHC Class I Peptide Loading from the Structure of the Tapasin-ERp57 Thiol Oxidoreductase Heterodimer. Immunity 2009, 30: 21-32. PMID: 19119025, PMCID: PMC2650231, DOI: 10.1016/j.immuni.2008.10.018.Peer-Reviewed Original Research
2008
The Structural Basis for Activation of the Rab Ypt1p by the TRAPP Membrane-Tethering Complexes
Cai Y, Chin HF, Lazarova D, Menon S, Fu C, Cai H, Sclafani A, Rodgers DW, De La Cruz EM, Ferro-Novick S, Reinisch KM. The Structural Basis for Activation of the Rab Ypt1p by the TRAPP Membrane-Tethering Complexes. Cell 2008, 133: 1202-1213. PMID: 18585354, PMCID: PMC2465810, DOI: 10.1016/j.cell.2008.04.049.Peer-Reviewed Original Research
2007
A Catalytic Coiled Coil: Structural Insights into the Activation of the Rab GTPase Sec4p by Sec2p
Dong G, Medkova M, Novick P, Reinisch KM. A Catalytic Coiled Coil: Structural Insights into the Activation of the Rab GTPase Sec4p by Sec2p. Molecular Cell 2007, 25: 455-462. PMID: 17289591, PMCID: PMC1847580, DOI: 10.1016/j.molcel.2007.01.013.Peer-Reviewed Original ResearchAmino Acid MotifsBinding SitesBiological TransportCrystallography, X-RayEnzyme ActivationGTP-Binding ProteinsGuanine Nucleotide Exchange FactorsModels, MolecularMolecular Sequence DataNucleotidesProtein Structure, TertiaryRab GTP-Binding ProteinsSaccharomyces cerevisiae ProteinsSequence AlignmentTransport Vesicles
2006
Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen
Fuchs G, Stein AJ, Fu C, Reinisch KM, Wolin SL. Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen. Nature Structural & Molecular Biology 2006, 13: 1002-1009. PMID: 17041599, DOI: 10.1038/nsmb1156.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensBase SequenceBinding SitesCrystallography, X-RayModels, MolecularMolecular Sequence DataMutagenesisNuclease Protection AssaysNucleic Acid ConformationOocytesProtein BindingProtein Structure, TertiaryRibonucleoproteinsRNA 3' End ProcessingRNA PrecursorsRNA-Binding ProteinsRNA, Ribosomal, 5SXenopus laevis
2005
The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif
Dong G, Hutagalung AH, Fu C, Novick P, Reinisch KM. The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif. Nature Structural & Molecular Biology 2005, 12: 1094-1100. PMID: 16249794, DOI: 10.1038/nsmb1017.Peer-Reviewed Original Research