2025
γ-secretase facilitates retromer-mediated retrograde transport
Takeo Y, Crite M, Mehmood K, DiMaio D. γ-secretase facilitates retromer-mediated retrograde transport. Journal Of Cell Science 2025, 138: jcs263538. PMID: 39865938, PMCID: PMC11883284, DOI: 10.1242/jcs.263538.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkTransport of protein cargoRetrograde protein traffickingCation-independent mannose-6-phosphate receptorCellular transmembrane proteinsMannose-6-phosphate receptorAssociation with cargoHuman epithelial cellsBinds retromerRetromer subunitsRetromer cargoRab7-GTPShiga toxinRetrograde transportCultured human epithelial cellsProtein traffickingRetromerCatalytic subunitTransmembrane domainTransmembrane proteinsProtein cargoCellular cargoTarget proteinsFunctional consequencesCholera toxin
2024
Upregulation vs. loss of function of NTRK2 in 44 affected individuals leads to two distinct neurodevelopmental disorders
Berger E, Jauss R, Ranells J, Zonic E, von Wintzingerode L, Wilson A, Wagner J, Tuttle A, Thomas-Wilson A, Schulte B, Rabin R, Pappas J, Odgis J, Muthaffar O, Mendez-Fadol A, Lynch M, Levy J, Lehalle D, Lake N, Krey I, Kozenko M, Knierim E, Jouret G, Jobanputra V, Isidor B, Hunt D, Hsieh T, Holtz A, Haack T, Gold N, Dunstheimer D, Donge M, Deb W, De La Rosa Poueriet K, Danyel M, Christodoulou J, Chopra S, Callewaert B, Busche A, Brick L, Bigay B, Arlt M, Anikar S, Almohammal M, Almanza D, Alhashem A, Bertoli-Avella A, Sticht H, Abou Jamra R. Upregulation vs. loss of function of NTRK2 in 44 affected individuals leads to two distinct neurodevelopmental disorders. Genetics In Medicine 2024, 101326. PMID: 39540377, DOI: 10.1016/j.gim.2024.101326.Peer-Reviewed Original ResearchDevelopmental delayHeterozygous pathogenic variantsTherapy-refractory epilepsyAffected individualsPhenotype of developmental delayDevelopmental delay/intellectual disabilityGlobal developmental delayRecurrent variant c.Associated with global developmental delayCholesterol-binding motifsTrkB activationVariant c.Pathogenic variantsMuscular hypotoniaFeeding difficultiesSevere phenotypeLoss of functionBinding motifVisual impairmentTransmembrane domainTruncating variantsNeurodevelopmental disordersNTRK2CohortVariantsAlternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions
Lee P, Sun Y, Soares A, Fai C, Picciotto M, Guo J. Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions. Molecular Cell 2024, 84: 3967-3978.e8. PMID: 39317199, PMCID: PMC11490368, DOI: 10.1016/j.molcel.2024.08.032.Peer-Reviewed Original ResearchTranslation initiation siteNeuronal pentraxin receptorAUG translational initiation siteAlternative translation initiation sitesN-terminal signal sequenceN-terminal transmembrane domainRNA secondary structureAlternative translation initiationN-terminal extensionTranslation initiationSignal sequenceProtein isoformsProtein localizationAUG initiatorTransmembrane domainWidespread mechanismSecondary structureInitiation siteAlternative usageAMPA-type glutamate receptorsProteoformsSecreted factorsProteinReduced AMPA receptorMRNAOverlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles
Park D, Fujise K, Wu Y, Luján R, Del Olmo-Cabrera S, Wesseling J, De Camilli P. Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2409605121. PMID: 38985768, PMCID: PMC11260120, DOI: 10.1073/pnas.2409605121.Peer-Reviewed Original ResearchConceptsSynaptic vesiclesFamily proteinsBiogenesis of synaptic vesiclesClusters of small vesiclesSize of synaptic vesiclesSynaptogyrin familySynaptogyrin-1Vesicle proteinsSynaptogyrinTransmembrane domainOrganismal levelSmall vesiclesProteinMild defectsVesiclesFamily membersBiogenesisSmall sizeFamilyMiceSynapsinCoexpressionAbundanceSynaptoporinMembers
2023
Allosteric inhibition of the T cell receptor by a designed membrane ligand
Ye Y, Morita S, Chang J, Buckley P, Wilhelm K, DiMaio D, Groves J, Barrera F. Allosteric inhibition of the T cell receptor by a designed membrane ligand. ELife 2023, 12: e82861. PMID: 37796108, PMCID: PMC10554751, DOI: 10.7554/elife.82861.Peer-Reviewed Original ResearchConceptsT cell receptorTCR activationCD3ζ subunitsTM ligandsComplex molecular machinesReceptor tyrosine kinase EphA2Cell receptorTM domainTransmembrane domainNative nanodiscsTCR subunitsAllosteric changesTM bundleCytoplasmic sideTM regionMolecular mechanismsExtracellular domainAllosteric inhibitionLck phosphorylationMolecular machinesMembrane receptorsAberrant activationSubunitsMembrane ligandsDecades of investigation
2022
The Get1/2 insertase forms a channel to mediate the insertion of tail-anchored proteins into the ER
Heo P, Culver J, Miao J, Pincet F, Mariappan M. The Get1/2 insertase forms a channel to mediate the insertion of tail-anchored proteins into the ER. Cell Reports 2022, 42: 111921. PMID: 36640319, PMCID: PMC9932932, DOI: 10.1016/j.celrep.2022.111921.Peer-Reviewed Original ResearchConceptsTransmembrane domainTA proteinsSingle C-terminal transmembrane domainC-terminal transmembrane domainTail-anchored (TA) proteinsTail-anchored proteinsEndoplasmic reticulum membraneGet3Reticulum membraneChannel functionInsertaseBulk fluorescenceAqueous channelsProteinChannel activityMutation analysisMembraneMicrofluidic assayTranslocaseYeastComplexesInsertionTranslocationHydrophilic segmentsBindingTransmembrane proteins tetraspanin 4 and CD9 sense membrane curvature
Dharan R, Goren S, Cheppali S, Shendrik P, Brand G, Vaknin A, Yu L, Kozlov M, Sorkin R. Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208993119. PMID: 36252000, PMCID: PMC9618112, DOI: 10.1073/pnas.2208993119.Peer-Reviewed Original ResearchConceptsRetraction fibersTetraspanin proteinsMigrasome formationMembrane curvatureSense membrane curvatureMembrane remodeling processesPositive membrane curvatureFamily of proteinsGiant plasma membrane vesiclesControl membrane tensionCurved membrane structuresOocyte microvilliCellular processesTransmembrane domainPlasma membrane vesiclesMembrane-shapingProteinCell typesMembrane vesiclesMembrane tensionTetraspaninCD9Membrane structureRemodeling processMembraneA Tripartite Efflux System Affects Flagellum Stability in Helicobacter pylori
Gibson K, Chu JK, Zhu S, Nguyen D, Mrázek J, Liu J, Hoover TR. A Tripartite Efflux System Affects Flagellum Stability in Helicobacter pylori. International Journal Of Molecular Sciences 2022, 23: 11609. PMID: 36232924, PMCID: PMC9570263, DOI: 10.3390/ijms231911609.Peer-Reviewed Original ResearchConceptsTripartite efflux systemEfflux systemPeriplasmic membrane fusion proteinOuter membrane efflux proteinCryo-electron tomography studiesMembrane efflux proteinMembrane fusion proteinNumber of flagellaTransmembrane domainABC transportersUnsheathed flagellaSwimming motilityCandidate proteinsFusion proteinEfflux proteinsSame frameshift mutationFlagellaEnhanced motilityMutantsFlagellar sheathFrameshift mutationProteinIndependent variantsHomologP ringPolybasic Patches in Both C2 Domains of Synaptotagmin-1 Are Required for Evoked Neurotransmitter Release
Wu Z, Ma L, Courtney NA, Zhu J, Landajuela A, Zhang Y, Chapman ER, Karatekin E. Polybasic Patches in Both C2 Domains of Synaptotagmin-1 Are Required for Evoked Neurotransmitter Release. Journal Of Neuroscience 2022, 42: 5816-5829. PMID: 35701163, PMCID: PMC9337609, DOI: 10.1523/jneurosci.1385-21.2022.Peer-Reviewed Original ResearchConceptsSynaptotagmin-1C2 domainSynchronous neurotransmitter releaseSNARE proteinsPlasma membraneCalcium sensorSingle-pass transmembrane domainOptical tweezers measurementsSynaptic vesiclesAcidic lipidsNeurotransmitter releaseBind calciumCharge neutralization mutationsEvoked Neurotransmitter ReleaseReleasable vesicle poolSyt1 functionSNARE complexPolybasic regionOverall affinityTransmembrane domainMembrane bindingSingle-molecule experimentsC2A domainSynchronous releaseVesicle poolStructural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide
Zhao Y, Roy K, Vidossich P, Cancedda L, De Vivo M, Forbush B, Cao E. Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide. Nature Communications 2022, 13: 2747. PMID: 35585053, PMCID: PMC9117670, DOI: 10.1038/s41467-022-30407-3.Peer-Reviewed Original ResearchConceptsTranslocation pathwayElectron cryo-microscopy structureC-terminal domainIon translocation pathwayCation-chloride cotransporters NKCC1Transmembrane domainCotransporter NKCC1C-terminal domain interactionsStructural basisDomain interactionsRenal salt reabsorptionDomain associationConformational changesFunctional studiesIon translocationElectroneutral symportCell membraneNKCC1PathwayNKCC2DomainSalt reabsorptionTransmembraneTranslocationTransportersClinical, Genetic and Functional Characterization of a Novel AVPR2 Missense Mutation in a Woman with X-Linked Recessive Nephrogenic Diabetes Insipidus
Selvaraj S, Rodrigues D, Krishnamoorthy N, Fakhro K, Saraiva L, Lemos M. Clinical, Genetic and Functional Characterization of a Novel AVPR2 Missense Mutation in a Woman with X-Linked Recessive Nephrogenic Diabetes Insipidus. Journal Of Personalized Medicine 2022, 12: 118. PMID: 35055433, PMCID: PMC8779739, DOI: 10.3390/jpm12010118.Peer-Reviewed Original ResearchNephrogenic diabetes insipidusX-linked recessive nephrogenic diabetes insipidusRecessive nephrogenic diabetes insipidusMissense mutationsAquaporin-2Diabetes insipidusIn silico protein modelingCongenital nephrogenic diabetes insipidusArginine vasopressin receptor 2Plasma membrane localizationVolumes of dilute urineAverage urinary outputAVPR2</i> geneDownstream intracellular signaling pathwaysHeterozygous missense mutationX-linked recessive inheritanceVasopressin receptor 2Intracellular signaling pathwaysHuman cellular modelsResponse to water deprivationX chromosomePhenotypic effectsGenetic analysisTransmembrane domainMembrane localizationSingle particle cryo-EM structure of the outer hair cell motor protein prestin
Butan C, Song Q, Bai JP, Tan WJT, Navaratnam D, Santos-Sacchi J. Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature Communications 2022, 13: 290. PMID: 35022426, PMCID: PMC8755724, DOI: 10.1038/s41467-021-27915-z.Peer-Reviewed Original ResearchConceptsTransmembrane domainProtein prestinSingle-particle cryo-EM structuresAnti-sigma factor antagonist domainOuter hair cell motor protein prestinCryo-EM structureCryo-electron microscopyMotor protein prestinSLC26 family membersSulfate transportersTransmembrane segmentsPrestin functionÅ resolutionPrestinOHC electromotilityOpen stateCochlear amplificationPutative mechanismsFamily membersDomainRepeatsSLC26A9TransportersMutationsElectromotility
2021
Cutaneous and hepatic vascular lesions due to a recurrent somatic GJA4 mutation reveal a pathway for vascular malformation
Ugwu N, Atzmony L, Ellis KT, Panse G, Jain D, Ko CJ, Nassiri N, Choate KA. Cutaneous and hepatic vascular lesions due to a recurrent somatic GJA4 mutation reveal a pathway for vascular malformation. Human Genetics And Genomics Advances 2021, 2: 100028. PMID: 33912852, PMCID: PMC8078848, DOI: 10.1016/j.xhgg.2021.100028.Peer-Reviewed Original ResearchSerum/glucocorticoid-regulated kinase 1Serine/threonine kinaseWhole-exome sequencingFirst transmembrane domainCell morphologyPrimary human endothelial cellsSomatic mutationsNon-canonical activationGlucocorticoid-regulated kinase 1Threonine kinaseTransmembrane domainEndothelial cellsSGK1 activationKinase 1Human endothelial cellsGenetic driversAlpha 4Lentiviral transductionInhibitors of angiogenesisSmooth muscle cellsMutationsCell proliferationSequencingUnrelated individualsSame mutation
2019
Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors
Sun L, Liu Y, Wang J, Huang L, Yang Y, Cheng X, Fan Y, Zhu M, Liang H, Tian Y, Wang H, Guo C, Yu Y. Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors. Journal Of Biological Chemistry 2019, 294: 19589-19603. PMID: 31727741, PMCID: PMC6926468, DOI: 10.1074/jbc.ra119.009959.Peer-Reviewed Original ResearchConceptsFuture transgenic studiesFull-length variantATP responseTransmembrane domainTransgenic studiesMammalian speciesP2X5 receptorsAllosteryPathological functionsSingle replacementSingle-channel recordingsSkeletal muscleExon 10Molecular modelingFunctional subtypesATPResiduesNervous systemP2X5ReceptorsDomainMammalsSpeciesTM2Lack of knowledgeSyndecan-1 Mediates Sorting of Soluble Lipoprotein Lipase with Sphingomyelin-Rich Membrane in the Golgi Apparatus
Sundberg EL, Deng Y, Burd CG. Syndecan-1 Mediates Sorting of Soluble Lipoprotein Lipase with Sphingomyelin-Rich Membrane in the Golgi Apparatus. Developmental Cell 2019, 51: 387-398.e4. PMID: 31543446, PMCID: PMC6832887, DOI: 10.1016/j.devcel.2019.08.014.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkSphingomyelin-rich membranesTransmembrane domainSecretory pathwayVesicular transport carriersIntegral membrane proteinsProtein transmembrane domainBiosynthetic secretory pathwaySyndecan-1Heparan sulfate chainsLipoprotein lipaseSorting receptorSecretion pathwayMembrane proteinsGolgi membranesProteoglycan syndecan-1Protein cargoSecretory vesiclesPlasma membraneGolgi apparatusSpecific sequencesTransport carriersSulfate chainsLipid compositionEnzyme lipoprotein lipaseTransmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit
He L, Cohen EB, Edwards APB, Xavier-Ferrucio J, Bugge K, Federman RS, Absher D, Myers RM, Kragelund BB, Krause DS, DiMaio D. Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit. IScience 2019, 17: 167-181. PMID: 31279934, PMCID: PMC6614117, DOI: 10.1016/j.isci.2019.06.027.Peer-Reviewed Original ResearchErythropoietin receptorPrimary human hematopoietic progenitor cellsProtein aptamerGrowth factor independenceHuman hematopoietic progenitor cellsJAK/STATMurine BaF3 cellsTransmembrane domainCellular processesCytoplasmic tyrosinesCytoplasmic domainHematopoietic progenitor cellsErythroid differentiationBaF3 cellsCommon subunitFactor independenceSerum withdrawalCell deathCooperative signalingEPO receptorEPOR homodimersProgenitor cellsEssential roleSubunitsSignaling
2018
S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi
Ernst AM, Syed SA, Zaki O, Bottanelli F, Zheng H, Hacke M, Xi Z, Rivera-Molina F, Graham M, Rebane AA, Björkholm P, Baddeley D, Toomre D, Pincet F, Rothman JE. S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi. Developmental Cell 2018, 47: 479-493.e7. PMID: 30458139, PMCID: PMC6251505, DOI: 10.1016/j.devcel.2018.10.024.Peer-Reviewed Original ResearchConceptsS-palmitoylationAnterograde cargoAnterograde signalMembrane cargoCargo selectionTransmembrane domainMembrane proteinsGolgi membranesGolgiSpecific signalsMembrane interfaceModel systemCargoProteinRate of transportAnterograde transportVesiclesCisternaeCurved regionsMembraneTransportRegionSignalsDomainFluorescence
2017
Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters
Matos-Cruz V, Schneider ER, Mastrotto M, Merriman DK, Bagriantsev SN, Gracheva EO. Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters. Cell Reports 2017, 21: 3329-3337. PMID: 29262313, PMCID: PMC5741102, DOI: 10.1016/j.celrep.2017.11.083.Peer-Reviewed Original ResearchConceptsTransmembrane domainCold toleranceCold sensitivityGround squirrelsRat orthologMolecular adaptationsMammalian hibernatorsReciprocal mutationsAmino acidsFunctional significanceOrthologsSquirrelsMolecular prerequisitesActive stateHibernatorsTRPM8Somatosensory neuronsTolerancePoor activationSpeciesDomainMutationsResiduesHibernationCellsStructural basis of MsbA-mediated lipopolysaccharide transport
Mi W, Li Y, Yoon SH, Ernst RK, Walz T, Liao M. Structural basis of MsbA-mediated lipopolysaccharide transport. Nature 2017, 549: 233-237. PMID: 28869968, PMCID: PMC5759761, DOI: 10.1038/nature23649.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateATP-Binding Cassette TransportersBacterial ProteinsBiological TransportCell MembraneCryoelectron MicroscopyEscherichia coliHydrophobic and Hydrophilic InteractionsLipid BilayersLipopolysaccharidesModels, MolecularNanostructuresPeriplasmProtein BindingProtein DomainsConceptsPeriplasmic leafletStructural basisSingle-particle cryo-electron microscopyCryo-electron microscopyÅ resolution structureLipid flippasesGram-negative bacteriaLipopolysaccharide transportTransmembrane domainInner membraneCytoplasmic leafletMsbAOuter membraneCell envelopeResolution structureCassette transportersADP-vanadateStructural mechanismsConformational transitionLPS recognitionFunctional stateFlippasesMsbA.Hydrophobic interactionsMembraneTwo transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation
Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM, DiMaio D. Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7262-e7271. PMID: 28808001, PMCID: PMC5584431, DOI: 10.1073/pnas.1705622114.Peer-Reviewed Original ResearchConceptsTransmembrane domainE5 proteinE5 dimerPlatelet-derived growth factor β receptorGrowth factor β receptorActive dimeric conformationPDGF β-receptorTransmembrane dimerProtein bindsMembrane environmentReceptor dimerizationDimeric conformationAtom molecular dynamics simulationsBiochemical experimentsMouse cellsMolecular mechanismsActive dimerΒ receptorBovine papillomavirusProteinSpecific interactionsMembrane modelingReceptor activationDimerizationComplexes
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply