2023
End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles
Park J, Xie Y, Miller K, De Camilli P, Yogev S. End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles. Current Biology 2023, 33: 3851-3864.e7. PMID: 37586371, PMCID: PMC10529979, DOI: 10.1016/j.cub.2023.07.052.Peer-Reviewed Original ResearchConceptsKIF1A/UNCTrans-GolgiDense-core vesiclesEnd-binding protein 1Microtubule growthEnd-binding protein EB1Calponin homology domainMicrotubule-associated proteinsDCV biogenesisCore vesiclesSorting machineryHomology domainAxonal deliveryProtein EB1DCV cargosEndogenous cargoUnrelated proteinsUnexpected roleFunction experimentsGolgiEarly stepsProtein 1UNCNeuronal functionProtein
2021
Identification of a Conserved Intracellular Loop (CIL) Structure That Scaffolds PIP3 to Amplify Oncogenic Signaling during Malignant B-Cell Transformation
Lee J, Robinson M, Ma N, Sadras T, Cosgun K, Chan L, Kume K, Thomas-Tikhonenko A, Weinstock D, Diamond M, Vaidehi N, Müschen M. Identification of a Conserved Intracellular Loop (CIL) Structure That Scaffolds PIP3 to Amplify Oncogenic Signaling during Malignant B-Cell Transformation. Blood 2021, 138: 868. DOI: 10.1182/blood-2021-149646.Peer-Reviewed Original ResearchLipid raftsB cell receptorB cell activationB cell activation signalsConstitutive membrane localizationMalignant B-cell transformationPleckstrin homology domainCell membrane lipid compositionMembrane lipid compositionNormal B-cell activationEndosomal proteinCell membrane lipidsBasic lysine residueHomology domainPH domainMembrane localizationB-cell transformationProteomic analysisEndosomal membranesPIP3PIP3 accumulationOncogenic signalingOncogenic transformationGene expressionInducible activation
2019
Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction
Li Z, Li L, Zhang H, Zhou HJ, Ji W, Min W. Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction. Arteriosclerosis Thrombosis And Vascular Biology 2019, 40: 112-127. PMID: 31619063, PMCID: PMC7204498, DOI: 10.1161/atvbaha.119.312976.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicApoptosisArteriosclerosisBlotting, WesternCells, CulturedDisease Models, AnimalDNAEndothelium, VascularGene Expression RegulationGenome-Wide Association StudyHumansMiceMice, Inbred C57BLMice, TransgenicMicroscopy, FluorescenceMitochondriaras GTPase-Activating ProteinsSignal TransductionConceptsN-terminal pleckstrin homology domainHuman genome-wide association studiesGenome-wide association studiesPleckstrin homology domainMitochondrial reactive oxygen species generationEndothelial cellsH3K9 trimethylationHomology domainReactive oxygen species productionOxygen species productionReactive oxygen speciesReactive oxygen species generationAssociation studiesRegulatory factorsEpigenetic inhibitionEC activationOxygen species generationDependent pathwayVascular endothelial cellsProteolytic degradationSpecies productionOxygen speciesVascular homeostasisMitochondriaSpecies generation
2018
Structural basis of the filamin A actin-binding domain interaction with F-actin
Iwamoto DV, Huehn A, Simon B, Huet-Calderwood C, Baldassarre M, Sindelar CV, Calderwood DA. Structural basis of the filamin A actin-binding domain interaction with F-actin. Nature Structural & Molecular Biology 2018, 25: 918-927. PMID: 30224736, PMCID: PMC6173970, DOI: 10.1038/s41594-018-0128-3.Peer-Reviewed Original ResearchConceptsActin-binding domainCalponin homology domainHomology domainF-actinActin cross-linking proteinFunction mutationsTandem calponin homology domainsDisease-associated mutantsCryo-electron microscopyHigh-resolution structuresNumerous genetic diseasesSequence conservationHigher-order structureLinking proteinStructural basisDomain interactionsCell shapeActin filamentsMolecular understandingN-terminalFunctional studiesGenetic diseasesMissense mutationsMutationsAtomic resolution
2017
Dimerization of Tie2 mediated by its membrane-proximal FNIII domains
Moore JO, Lemmon MA, Ferguson KM. Dimerization of Tie2 mediated by its membrane-proximal FNIII domains. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 4382-4387. PMID: 28396397, PMCID: PMC5410832, DOI: 10.1073/pnas.1617800114.Peer-Reviewed Original ResearchConceptsExtracellular regionFNIII domainsResolution X-ray crystal structureMembrane-proximal fibronectin type III domainsDomain-mediated interactionsDifferent cellular contextsLigand-binding regionHigher-order oligomersTie2 activationFibronectin type III domainReceptor tyrosine kinasesTyrosine kinase familyEGF-homology domainThird FNIII domainType III domainPrevious structural studiesStructural studiesHomology domainCellular contextKinase familyDimer interfaceDimerization modeReceptor dimerizationTyrosine kinasePrimary activator
2015
PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts
Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, De Camilli P. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts. Science 2015, 349: 428-432. PMID: 26206935, PMCID: PMC4638224, DOI: 10.1126/science.aab1370.Peer-Reviewed Original ResearchConceptsPlasma membraneEndoplasmic reticulumER integral membrane proteinsER–plasma membrane contactsMembrane lipid homeostasisIntegral membrane proteinsPleckstrin homology domainOxysterol-binding proteinPI4P phosphatase Sac1PI4P levelsCell membrane bilayerHomology domainPhosphatase Sac1Membrane proteinsORP8Function experimentsMembrane bilayerLipid homeostasisLipid transferProtein 5Membrane contactORP5PI4PPhosphatidylserineProteinCCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation
Draheim KM, Li X, Zhang R, Fisher OS, Villari G, Boggon TJ, Calderwood DA. CCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation. Journal Of Cell Biology 2015, 208: 987-1001. PMID: 25825518, PMCID: PMC4384732, DOI: 10.1083/jcb.201407129.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBinding SitesCarrier ProteinsCell LineCell ProliferationCentral Nervous SystemCrystallography, X-RayGene ExpressionHemangioma, Cavernous, Central Nervous SystemHumansMembrane ProteinsMutagenesisNeovascularization, PhysiologicPaxillinProtein BindingProtein Interaction MappingProtein Structure, TertiaryProteolysisProto-Oncogene ProteinsRNA InterferenceRNA, Small InterferingSequence AlignmentConceptsBinding-deficient mutantStructure-guided mutagenesisNormal cell growthCerebral cavernous malformationsEndothelial network formationHomology domainCCM3 proteinsProteasomal degradationEndothelial cell network formationMolecular basisCell network formationEssential adaptorCell growthFunctional significanceCCM3 expressionX-ray crystallographyProtein expressionCCM2CCM3Network formationExpressionMutantsHP1MutagenesisAdaptorDirect Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*
Simpson MA, Bradley WD, Harburger D, Parsons M, Calderwood DA, Koleske AJ. Direct Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*. Journal Of Biological Chemistry 2015, 290: 8360-8372. PMID: 25694433, PMCID: PMC4375489, DOI: 10.1074/jbc.m115.638874.Peer-Reviewed Original ResearchConceptsIntegrin β1 cytoplasmic tailExtracellular matrix adhesion receptorsSrc homology domainFibroblast cell motilityIntegrin β1Β1 cytoplasmic tailMembrane-proximal segmentAdhesion complex formationMatrix adhesion receptorsNonreceptor tyrosine kinaseArg kinase activityArg nonreceptor tyrosine kinaseCancer cell invasivenessHomology domainActin cytoskeletonCytoplasmic tailCytoskeletal remodelingDendrite morphogenesisTyr-783Kinase domainPhosphorylated regionAbl familyΒ1 tailArg kinaseCell motility
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 sclerosis
2012
Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin
MacGrath SM, Koleske AJ. Arg/Abl2 Modulates the Affinity and Stoichiometry of Binding of Cortactin to F‑Actin. Biochemistry 2012, 51: 6644-6653. PMID: 22849492, PMCID: PMC3556572, DOI: 10.1021/bi300722t.Peer-Reviewed Original ResearchConceptsStoichiometry of bindingF-actinTerminal calponin homology domainRecruitment of cortactinActin cosedimentation assaysArp2/3 complex activatorsCell edge protrusionActin network assemblyCalponin homology domainProtein-protein interactionsCortactin bindsHomology domainActin cytoskeletonArg CDeletion mutantsCosedimentation assaysFilamentous actinEdge protrusionComplex activatorActin binding propertiesCortactinActin filamentsNetwork assemblyDownstream effectsBindingStructural Basis for Paxillin Binding and Focal Adhesion Targeting of β-Parvin*
Stiegler AL, Draheim KM, Li X, Chayen NE, Calderwood DA, Boggon TJ. Structural Basis for Paxillin Binding and Focal Adhesion Targeting of β-Parvin*. Journal Of Biological Chemistry 2012, 287: 32566-32577. PMID: 22869380, PMCID: PMC3463362, DOI: 10.1074/jbc.m112.367342.Peer-Reviewed Original ResearchConceptsΒ-parvinFocal adhesionsPaxillin bindingΑ-parvinFocal adhesion targetingN-terminal α-helixPaxillin LD1 motifCalponin homology domainFirst molecular detailsHigh sequence similarityCytoplasmic adaptor proteinIntegrin-linked kinasePaxillin LD1Co-crystal structureLD4 motifSignificant conformational flexibilityHomology domainAdaptor proteinCellular functionsSequence similarityRepeat motifsProper localizationMolecular detailsPaxillinStructural basis
2011
Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt
Troutman T, Hu W, Fulenchek S, Yamazaki T, Kurosaki T, Bazan J, Pasare C. Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 109: 273-278. PMID: 22187460, PMCID: PMC3252926, DOI: 10.1073/pnas.1118579109.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsB-LymphocytesEnzyme ActivationHEK293 CellsHumansInflammationMacrophagesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMyeloid Differentiation Factor 88Phosphatidylinositol 3-KinasesProtein Structure, TertiaryProto-Oncogene Proteins c-aktSignal TransductionToll-Like ReceptorsConceptsToll-IL-1 receptorToll-like receptorsB-cell adapterPI3KSignaling to activationSusceptibility to dextran sulfate sodium-induced colitisActivation of transcription factorsActivation of PI3KB cellsToll-IL-1 receptor domain-containing adapterRecruitment of inflammatory myeloid cellsToll-like receptor signalingPI3K activitySignal adaptationTLR signaling pathwaysIFN regulatory factorPrimary response geneToll-like receptor stimulationDextran sulfate sodium-induced colitisInflammatory myeloid cellsInduce activation of transcription factorsMyeloid differentiation primary response geneHomology domainDifferentiation primary response geneTranscription factors
2010
Dlxin-1, a MAGE family protein, induces accelerated neurite outgrowth and cell survival by enhanced and early activation of MEK and Akt signalling pathways in PC12 cells
Reddy E, Chettiar S, Kaur N, Shepal V, Shiras A. Dlxin-1, a MAGE family protein, induces accelerated neurite outgrowth and cell survival by enhanced and early activation of MEK and Akt signalling pathways in PC12 cells. Experimental Cell Research 2010, 316: 2220-2236. PMID: 20595047, DOI: 10.1016/j.yexcr.2010.05.030.Peer-Reviewed Original ResearchConceptsDlxin-1MAGE homology domainCell survivalPC12 cellsPresence of NGFNeuronal differentiationDiverse cellular functionsMAGE family proteinsCell cycle progressionTranscriptional regulationHomology domainCellular functionsFamily proteinsNeuronal survivalDevelopmental apoptosisEnhanced neuritogenesisCycle progressionSignaling pathwaysMEK pathwayPharmacological inhibitorsCell deathAkt pathwayUnique regionAmino acidsEarly activationCrystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity*
Li X, Zhang R, Zhang H, He Y, Ji W, Min W, Boggon TJ. Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity*. Journal Of Biological Chemistry 2010, 285: 24099-24107. PMID: 20489202, PMCID: PMC2911348, DOI: 10.1074/jbc.m110.128470.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBinding, CompetitiveBrainCrystallography, X-RayDimerizationHemangioma, Cavernous, Central Nervous SystemHumansKineticsMembrane ProteinsMolecular ConformationMutationPaxillinProtein ConformationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiaryProto-Oncogene ProteinsConceptsN-terminal dimerization domainPaxillin LD motifsCerebral cavernous malformationsAlpha-helical proteinsLD motifsCCM complexHomology domainFocal adhesionsDimerization domainMolecular basisHydrophobic pocketHuman populationCCM3 mutationsMutationsCCM3Crystal structureVascular integrityCCM2DomainPaxillinProteinMotifCCM1InteractionCellsChapter 136 Pleckstrin Homology (PH) Domains
Lemmon M. Chapter 136 Pleckstrin Homology (PH) Domains. 2010, 1093-1101. DOI: 10.1016/b978-0-12-374145-5.00136-4.Peer-Reviewed Original ResearchPleckstrin homology domainPH domainHomology domainPH domain-containing proteinsDifferent PH domainsDomain-containing proteinsReceptor-mediated endocytosisParticular phosphoinositidesMembrane traffickingMembrane associationProtein functionSequence similarityCommon foldCellular signalingCytoskeletal organizationFunctional relatednessProtein targetsPhosphoinositidePhysiological rolePhysiological relevancePromiscuous bindingX-ray crystallographyPhospholipid modificationStructural similarityProtein
2009
CVP2‐ and CVL1‐mediated phosphoinositide signaling as a regulator of the ARF GAP SFC/VAN3 in establishment of foliar vein patterns
Carland F, Nelson T. CVP2‐ and CVL1‐mediated phosphoinositide signaling as a regulator of the ARF GAP SFC/VAN3 in establishment of foliar vein patterns. The Plant Journal 2009, 59: 895-907. PMID: 19473324, DOI: 10.1111/j.1365-313x.2009.03920.x.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainVein phenotypeCell polarityHomology domainSpecific phosphoinositideADP-ribosylation factor GTPaseVein pattern formationIntracellular vesicle transportPlant ArabidopsisVesicle trafficLeaf developmentVesicle cargoVesicle transportVAN3Animal cellsFoliar organsPhosphoinositidePi-ligandCellular sitesMutantsPattern formationMutationsCvp2PhenotypeRecent evidenceA possible effector role for the pleckstrin homology (PH) domain of dynamin
Bethoney KA, King MC, Hinshaw JE, Ostap EM, Lemmon MA. A possible effector role for the pleckstrin homology (PH) domain of dynamin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13359-13364. PMID: 19666604, PMCID: PMC2720410, DOI: 10.1073/pnas.0906945106.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainHomology domainPH domainAbility of dynaminLarge GTPase dynaminPH domain mutationsPhosphoinositide-containing membranesGTPase dynaminDynamin functionVesicle scissionMembrane scissionDynamin helixDynamin assemblyTargeting roleDynamin oligomersDynamin 1Possible effector roleAnimal cellsBisphosphate moleculesActin polymerizationDynaminClathrinDomain mutationsPhosphoinositideEndocytosisAuto‐inhibition of dynamin GTPase activity is regulated by PH domain interactions
Kenniston J, Lemmon M. Auto‐inhibition of dynamin GTPase activity is regulated by PH domain interactions. The FASEB Journal 2009, 23: 697.3-697.3. DOI: 10.1096/fasebj.23.1_supplement.697.3.Peer-Reviewed Original ResearchGTPase activityDynamin pleckstrin homology domainDynamin GTPase activityPleckstrin homology domainGTP hydrolysis ratePH domain interactionJane Coffin Childs Memorial FundReceptor-mediated endocytosisGTPase domainHomology domainDynamin GTPaseInteraction motifsGTP hydrolysisAbsence of lipidsConformational interplaySelective mutagenesisDomain interactionsGTPase rateVesicle interactionsDynaminScission eventsDistinct groupsGTPaseMutagenesisEndocytosis
2008
Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors
Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors. Science 2008, 320: 1651-1654. PMID: 18566289, PMCID: PMC2514061, DOI: 10.1126/science.1158160.Peer-Reviewed Original ResearchConceptsSecretion systemL. pneumophila-containing vacuoleIntracellular pathogen Legionella pneumophilaHost cellsDifferent bacterial proteinsType IV secretion systemMicrotubule-dependent vesicular transportEukaryotic host cellsType IV effectorsPathogen Legionella pneumophilaSpecialized secretion systemsAnkyrin Repeat ProteinsANK proteinsEukaryotic cellsHomology domainEffector proteinsEukaryotic factorsRepeat proteinsInfection of macrophagesVesicular transportBacterial proteinsLate endosomesDiverse familyProteinLegionella pneumophilaStructural and biochemical characterization of the KRLB region in insulin receptor substrate-2
Wu J, Tseng Y, Xu C, Neubert T, White M, Hubbard S. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nature Structural & Molecular Biology 2008, 15: 251-258. PMID: 18278056, DOI: 10.1038/nsmb.1388.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsCricetinaeCricetulusCrystallography, X-RayHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceModels, MolecularMolecular Sequence DataMutationPhosphoproteinsPhosphorylationPhosphotyrosineProtein BindingProtein Structure, TertiaryProtein-Tyrosine KinasesReceptor, IGF Type 1Structure-Activity RelationshipSubstrate SpecificityConceptsInsulin receptorPleckstrin homology domainCrucial adaptor proteinTwo-hybrid studiesInsulin receptor kinaseKinase active siteInsulin receptor substrate 2C-terminal regionTyrosine kinase domainPrevious yeastThreonine phosphorylationHomology domainAdaptor proteinReceptor kinaseKinase domainTyrosine phosphorylationBiochemical characterizationRegion functionsSubstrate 2Binding regionsPhosphorylationKinase inhibitionFactor 1IRS2Insulin-like growth factor-1
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