2025
Key challenges and recommendations for defining organelle membrane contact sites
Calì T, Bayer E, Eden E, Hajnóczky G, Kornmann B, Lackner L, Liou J, Reinisch K, Rhee H, Rizzuto R, Scorrano L, Brini M. Key challenges and recommendations for defining organelle membrane contact sites. Nature Reviews Molecular Cell Biology 2025, 1-21. PMID: 40550870, DOI: 10.1038/s41580-025-00864-x.Peer-Reviewed Original ResearchMembrane contact sitesContact sitesContact site formationMembrane-bound compartmentsOrganelle interactionsTethering proteinsExtracellular stimuliCellular functionsCellular signalingSuper-resolution microscopyProteomic approachReporter constructsMolecular playersSite dynamicsOrganellesSite formationProteinPhysiological conditionsElectron tomographyExperimental approachExchange of ionsSitesPathological conditionsGeneticsMass spectrometryCerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease
Mecca A, Ashton N, Chen M, O'Dell R, Toyonaga T, Zhao W, Young J, Salardini E, Bates K, Ra J, Goodcase S, Silva‐Rudberg J, Nabulsi N, Brinkmalm A, Kvartsberg H, Schöll M, Nilsson J, Arnsten A, Huang Y, Hansson O, Zetterberg H, Carson R, Blennow K, van Dyck C. Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease. Alzheimer's & Dementia 2025, 21: e70344. PMID: 40491249, PMCID: PMC12149441, DOI: 10.1002/alz.70344.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2APositron emission tomographyAlzheimer's diseaseSynaptic densityEnzyme-linked immunosorbent assayC]UCB-J positron emission tomographyPositron emission tomography measurementsEmission tomographyAxonal proteinsCN participantsImmunosorbent assaySymptomatic Alzheimer's diseaseAD groupProteinAssayParticipantsSV2AAlzheimerCerebrospinal fluidBrainInvestigate associationsCerebrospinal fluid assaysSV2A positron emission tomographyTransgenic expression of endoplasmic reticulum proteins in C. elegans neurons is prone to causing ER stress
Park J, Yogev S. Transgenic expression of endoplasmic reticulum proteins in C. elegans neurons is prone to causing ER stress. MicroPublication Biology 2025, 2025: 10.17912/micropub.biology.001547. PMID: 40519643, PMCID: PMC12163624, DOI: 10.17912/micropub.biology.001547.Peer-Reviewed Original ResearchER-associated degradationER stressLevels of ER stressOrganelle-specific markersC. elegans neuronsEndoplasmic reticulum proteinEndomembrane systemOrganelle biologyOrganelle markersIndividual organellesFluorescent proteinTransgenic markersOrganellesProteinPhenotypeMarkersEndomembraneExpressionTransgene expressionLow levelsBiologyStressER tubular body: an ER-derived compartment for redirecting autophagy to secretory functions
Song M, Sim H, Noh S, Malhotra V, Lee M. ER tubular body: an ER-derived compartment for redirecting autophagy to secretory functions. Autophagy 2025, ahead-of-print: 1-3. PMID: 40390263, DOI: 10.1080/15548627.2025.2508935.Peer-Reviewed Original ResearchPositive-strand RNA virusesConditions of cellular stressFormation of membrane compartmentsER-derived compartmentSecretion of proteinsCell surface traffickingReticulophagy receptorER remodelingVesicle traffickingProtein homeostasisMembrane compartmentsEndoplasmic reticulumActivation of UCPRNA virusesTransmembrane proteinsCellular stressProtein secretionTrafficking defectTubulovesicular networkPotential therapeutic strategyViral pathogenesisProteinViral replicationSecretory functionTubular bodyImplications for OLE RNA as a natural integral membrane RNA.
Lyon S, Breaker R. Implications for OLE RNA as a natural integral membrane RNA. RNA 2025, rna.080489.125. PMID: 40393771, DOI: 10.1261/rna.080489.125.Peer-Reviewed Original ResearchOLE RNARNA world organismsGram-positive bacterial speciesCellular stress responseEmergence of proteinsBacterial hostsLocalized to cell membranesBilayer of membranesRibonucleoprotein complexMaster regulatorsBacterial speciesBiochemical functionsEvolutionary emergenceStress responseRNANoncoding RNAsRNA polymersCell membraneUnusual classPhospholipid bilayersRibonucleoproteinMembraneProteinSpeciesOrnateA triple-action inhibitory mechanism of allosteric TYK2-specific inhibitors
Wang J, Lomakin I, Batista V, Bunick C. A triple-action inhibitory mechanism of allosteric TYK2-specific inhibitors. Journal Of Investigative Dermatology 2025 PMID: 40378946, DOI: 10.1016/j.jid.2025.04.025.Peer-Reviewed Original ResearchJak-signal transducer and activatorAutoinhibited statePseudokinase domainIFN-induced gene expressionAtomic resolution structuresPhosphorylation of downstream proteinsAdenosine triphosphate bindingTyk2 kinaseTriphosphate bindingKinase domainActive stateResolution structureKinase activityTyk2Gene expressionStructural basisDownstream proteinsAllosteric drugsSteric clashesAllosteric inhibitorsInhibition mechanismMechanistic hypothesesKinaseBindingProteinStructural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin
Kim M, Kim J, Lee G, Olinares P, Airan Y, Chow J, Park J, Jeong Y, Park J, Chait B, Herzon S, Kim C, Kang J. Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin. Structure 2025 PMID: 40381618, DOI: 10.1016/j.str.2025.04.017.Peer-Reviewed Original ResearchNRPS-PKSCarrier proteinCryo-EM structurePKS enzymesPolyketide synthaseBiosynthesis mechanismBiosynthetic enzymesUpstream enzymesDimer interfaceColibactinBinding sitesDocking interactionsKetosynthasePromote colorectal cancerEnzymeStructural studiesGenomeBiosynthesisStructural detailsStructural analysisProteinGenotoxinsSynthaseHostCLBICell-Free Protein Synthesis as a Method to Rapidly Screen Machine Learning-Generated Protease Variants
Thornton E, Boyle J, Laohakunakorn N, Regan L. Cell-Free Protein Synthesis as a Method to Rapidly Screen Machine Learning-Generated Protease Variants. ACS Synthetic Biology 2025, 14: 1710-1718. PMID: 40304425, PMCID: PMC12090339, DOI: 10.1021/acssynbio.5c00062.Peer-Reviewed Original ResearchHuman and pathogen-encoded circular RNAs in viral infections: insights into functions and therapeutic opportunities
Mueller N, Dujsikova A, Singh A, Chen Y. Human and pathogen-encoded circular RNAs in viral infections: insights into functions and therapeutic opportunities. Human Molecular Genetics 2025, ddaf031. PMID: 40304711, DOI: 10.1093/hmg/ddaf031.Peer-Reviewed Original ResearchDNA virusesHost cellular machineryHost-virus interactionsCircular RNAsContribution to pathogenesisRNA biologyProtein translationCellular machineryProtein decoysRNA-based therapiesBiological rolePotential of circRNAsRegulatory moleculesRNAMicroRNA spongesViral systemsDNAViral replicationImmune evasionTherapeutic targetCircRNAsTherapeutic opportunitiesHostProteinViral diseasesA compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease
de Geus M, Nairn A, Arnold S, Carlyle B. A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease. Brain Communications 2025, 7: fcaf202. PMID: 40491829, PMCID: PMC12146149, DOI: 10.1093/braincomms/fcaf202.Peer-Reviewed Original ResearchDifferentially expressed proteinsExpressed proteinsAlzheimer's diseaseReactive oxygen speciesFunctional enrichment analysisHeterogeneity of Alzheimer's diseaseAmyloid-bAlzheimer's disease cerebrospinal fluidAlzheimer's disease pathologyAlzheimer's disease datasetProteomic dataProteomic landscapeTau accumulationEnrichment analysisMetabolic regulationOmics studiesCerebrospinal fluid proteomeProtein changesProteinNeurodegenerative disordersDiverse mechanismsSynaptic signal processingDisease pathologyGlutathione metabolismOxygen speciesStructural and functional significance of Aedes aegypti AgBR1 flavivirus immunomodulator
Martinez-Castillo A, Barriales D, Azkargorta M, Zalamea J, Ardá A, Jimenez-Barbero J, Gonzalez-Lopez M, Aransay A, Marín-López A, Fikrig E, Elortza F, Anguita J, Abrescia N. Structural and functional significance of Aedes aegypti AgBR1 flavivirus immunomodulator. Journal Of Virology 2025, 99: e01878-24. PMID: 40272158, PMCID: PMC12090808, DOI: 10.1128/jvi.01878-24.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsGland proteinsMosquito-borne virusesFunctional significanceHost-cell responsesMosquito salivary gland proteinsProtein functionMosquito proteinsFunctional insightsThree-dimensional structureMurine primary macrophagesZika virusA-resolutionEnzymatic activityInfluence virus transmissionProteinBlood feedingCross-talkVirus entrySpread of mosquito-borne diseasesPrimary macrophagesCell proliferationInteraction studiesViral replicationPrevent Zika virusFlgY, PflA, and PflB form a spoke–ring network in the high-torque flagellar motor of Helicobacter pylori
Tachiyama S, Rosinke K, Khan M, Zhou X, Xin Y, Botting J, Yue J, Roujeinikova A, Hoover T, Liu J. FlgY, PflA, and PflB form a spoke–ring network in the high-torque flagellar motor of Helicobacter pylori. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2421632122. PMID: 40261933, PMCID: PMC12054838, DOI: 10.1073/pnas.2421632122.Peer-Reviewed Original ResearchConceptsMS ringAccessory proteinsStator complexWild-type <i>H. pyFlagellar motorSalmonella enterica</i>Protein-protein interactionsFlagellar motilityAlphaFold-predicted structuresFlgIBiochemical approachesPflBGastric mucus layerMolecular geneticsPFLACryoelectron tomographyUnique motilityBacterial flagellar motorMucus layerMotilityBacteriaProteinHuman stomachPseudoatomic modelHelicobacter pyloriBroxyquinoline targets NLRP3 to inhibit inflammasome activation and alleviate NLRP3-associated inflammatory diseases
Tang H, Zou X, Chen P, Wang Y, Gao S, Wang T, Xu Y, Ji S. Broxyquinoline targets NLRP3 to inhibit inflammasome activation and alleviate NLRP3-associated inflammatory diseases. International Immunopharmacology 2025, 156: 114687. PMID: 40253767, DOI: 10.1016/j.intimp.2025.114687.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisNLR family pyrin domain-containing 3Inflammasome activationInflammatory diseasesASC speck formationInflammasome-associated diseasesNEK7-NLRP3 interactionDamage signalingNF-kB pathwayHost defensePyrin domain-containing 3Speck formationAIM2 inflammasome activationActivation of NLRP3 inflammasomeFamily pyrin domain-containing 3Autoimmune encephalomyelitisMurine modelInterleukin-1bIL-1BInhibiting inflammasome activationNLRP3 inflammasome inhibitorAntimicrobial drugsNF-kBProteinTherapeutic agentsWeak, specific chemical interactions dictate barnase stability in diverse cellular environments
Tahir U, Davis C. Weak, specific chemical interactions dictate barnase stability in diverse cellular environments. Protein Science 2025, 34: e70128. PMID: 40248880, PMCID: PMC12006822, DOI: 10.1002/pro.70128.Peer-Reviewed Original ResearchConceptsCellular environmentMacromolecular crowdingFast relaxation imagingUnfolded stateDiverse cellular environmentsProteins in situProtein folding modelBacterial ribonucleaseU2-OS cellsProtein interactionsProtein stabilityNuclear lysatesHost organismBacterial cellsSmall proteinsIn vitroIntracellular compartmentsLarger proteinsBarnaseProteinNative environmentBiologically relevant environmentsCytoplasmSpecific interactionsIn-cellCrystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling
Li T, Stayrook S, Li W, Wang Y, Li H, Zhang J, Liu Y, Klein D. Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling. Nature Communications 2025, 16: 3580. PMID: 40234450, PMCID: PMC12000326, DOI: 10.1038/s41467-025-58828-w.Peer-Reviewed Original ResearchConceptsThrombospondin type I repeatsIsthmin-1Pre-adipocytesType I repeatsBacterial streptavidinSurface helicesI repeatsMolecular detailsDiverse functionsFunctional studiesAkt phosphorylationFunctional roleStructural plasticityInsulin-like propertiesCrystal structureAMOPGrowth factorDomainPhosphorylationApoptosisLiver steatosisProteinHelixAktStreptavidinThe bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage
Wang X, Xu P, Bentley-DeSousa A, Hancock-Cerutti W, Cai S, Johnson B, Tonelli F, Shao L, Talaia G, Alessi D, Ferguson S, De Camilli P. The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage. Nature Cell Biology 2025, 27: 776-789. PMID: 40211074, PMCID: PMC12081312, DOI: 10.1038/s41556-025-01653-6.Peer-Reviewed Original ResearchConceptsDisease genesResponse to lysosomal damageSurface of lysosomesER–lysosome contactsParkinson's disease genesDelivery to lysosomesLipid transport proteinsLysosomal damageVPS13 proteinsLysosomal surfaceDisease proteinsGenetic studiesDamaged lysosomesVPS13CLysosomal stressLipid transportLysosomesInhibited stateMembrane perturbationRab7Lysosomal dysfunctionProteinVps13LipidGenesGrowth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer’s dementia continuum: an [18 F] AV-45 study
Nemati R, Sohrabi-Ashlaghi A, Saberian P, Sadeghi M, Mardani S, Abadi A, Yaghoobpoor A, Heydari A, Khoshroo N, Rahnama Y, Mayeli M, Nasiri H. Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer’s dementia continuum: an [18 F] AV-45 study. BMC Neurology 2025, 25: 134. PMID: 40170060, PMCID: PMC11959801, DOI: 10.1186/s12883-025-04140-5.Peer-Reviewed Original ResearchConceptsAssociated with Alzheimer's diseaseMild cognitive impairmentMild cognitive impairment groupStandardized uptake value ratioAlzheimer's Disease Neuroimaging InitiativePET standardized uptake value ratioEarly stages of ADAmyloid-betaGAP-43Tau pathologyGAP-43 levelsAssociated proteinSynaptic dysfunctionStages of ADAV-45Mild cognitive impairment stageBrain amyloidosisAlzheimer's diseaseDementia continuumCognitive impairmentProtein 43Synaptic plasticityDiagnosis of ADProteinGrowth-associated proteinRelationship between Immunogenicity and Protein Structure at Amino Acid Substitution Sites of Blood Group Antigens
Howe J, Stack G. Relationship between Immunogenicity and Protein Structure at Amino Acid Substitution Sites of Blood Group Antigens. Blood 2025 PMID: 40163810, DOI: 10.1182/blood.2024025071.Peer-Reviewed Original ResearchProtein structureAa substitutionsBlood group antigensThree-dimensional protein structuresAmino acid substitution sitesAmino acidsGroup antigensSurface-accessible loopsInvestigating protein structureStructure predictionProtein regionsB strandsTertiary structureFlexible regionsInformatics analysisAlphaFold2ProteinAminoImmunogenic antigensSitesDeterminants of immunogenicitySubstitutionPolypeptideConfidence scoresDisordered coilsTurnover atlas of proteome and phosphoproteome across mouse tissues and brain regions
Li W, Dasgupta A, Yang K, Wang S, Hemandhar-Kumar N, Chepyala S, Yarbro J, Hu Z, Salovska B, Fornasiero E, Peng J, Liu Y. Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions. Cell 2025, 188: 2267-2287.e21. PMID: 40118046, PMCID: PMC12033170, DOI: 10.1016/j.cell.2025.02.021.Peer-Reviewed Original ResearchConceptsMouse tissuesNeurodegeneration-related proteinsPost-translational modificationsImpact of phosphorylationStable isotope labelingLong-lived proteinsPeroxisomal proteinsProtein lifetimeProteomic propertiesProtein phosphorylationProtein stabilityInteractive web-based portalProtein abundanceProtein turnoverPhosphorylationMammalian tissuesComprehensive resourceProteinIsotope labelingProteomicsA-synucleinAbundanceTurnoverTurnover changesPhosphositesMultimodal MRI accurately identifies amyloid status in unbalanced cohorts in Alzheimer’s disease continuum
Dolci G, Ellis C, Cruciani F, Brusini L, Abrol A, Galazzo I, Menegaz G, Calhoun V, Initiative F. Multimodal MRI accurately identifies amyloid status in unbalanced cohorts in Alzheimer’s disease continuum. Network Neuroscience 2025, 9: 259-279. PMID: 40161995, PMCID: PMC11949592, DOI: 10.1162/netn_a_00423.Peer-Reviewed Original ResearchNeuropathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseHyperphosphorylated tau proteinAmyloid-bTau proteinNeurofibrillary tanglesNeuropathological hallmarksAmyloid accumulationAlzheimer's diseaseAb accumulationDepositional signatureIdentification of individualsAmyloid statusAccumulationAmyloidShed lightTanglesAlzheimer's disease continuumProtein
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