2023
Metformin inhibits digestive proteases and impairs protein digestion in mice
Kelly C, Verdegaal A, Anderson B, Shaw W, Bencivenga-Barry N, Folta-Stogniew E, Goodman A. Metformin inhibits digestive proteases and impairs protein digestion in mice. Journal Of Biological Chemistry 2023, 299: 105363. PMID: 37863262, PMCID: PMC10663847, DOI: 10.1016/j.jbc.2023.105363.Peer-Reviewed Original ResearchConceptsGastrointestinal side effectsSide effectsDrug concentrationsDaily metformin doseFirst-line therapyType 2 diabetesEnteropeptidase activityPrescribed medicationsMetformin doseIntestinal lumenGastrointestinal tissuesMice exhibitMetforminProtein maldigestionHuman duodenumProtein digestionTrypsin activityDigestive enzymesMedicationsDiabetesMaldigestionDuodenumTherapyActivityMiceIron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection
Spiga L, Fansler R, Perera Y, Shealy N, Munneke M, David H, Torres T, Lemoff A, Ran X, Richardson K, Pudlo N, Martens E, Folta-Stogniew E, Yang Z, Skaar E, Byndloss M, Chazin W, Zhu W. Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection. Cell Host & Microbe 2023, 31: 1639-1654.e10. PMID: 37776864, PMCID: PMC10599249, DOI: 10.1016/j.chom.2023.08.018.Peer-Reviewed Original ResearchConceptsLipocalin-2Nutritional immunityProtein lipocalin 2Role of commensalIntestinal inflammationInflamed gutSalmonella infectionHost nutritional immunityImmunityGut bacteriaIron metabolismHost-pathogen interactionsGut commensal Bacteroides thetaiotaomicronPathogensBacteroides thetaiotaomicronSalmonellaInflammationInfectionHost sequestrationGenetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Lee S, Schleer H, Park H, Jang E, Boyer M, Tao B, Gamez-Mendez A, Singh A, Folta-Stogniew E, Zhang X, Qin L, Xiao X, Xu L, Zhang J, Hu X, Pashos E, Tellides G, Shaul P, Lee W, Fernandez-Hernando C, Eichmann A, Sessa W. Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2023, 2: 438-448. PMID: 39196046, PMCID: PMC11358031, DOI: 10.1038/s44161-023-00266-2.Peer-Reviewed Original ResearchLDL transcytosisLDL receptor knockout miceReceptor knockout miceAtherosclerotic cardiovascular diseaseLow-density lipoprotein accumulationHigh-fat dietPromising therapeutic strategyTherapeutic neutralizationMacrophage infiltrationTriglyceride levelsLDL entryCardiovascular diseaseSelective monoclonal antibodiesLipoprotein accumulationTherapeutic strategiesKnockout micePlaque formationAtherosclerosis initiationType 1Genetic deletionArterial wallMonoclonal antibodiesEndothelial cellsLDL accumulationMice
2022
Gut Commensal Bacteroidetes Encode a Novel Class of Vitamin B12-Binding Proteins
Putnam EE, Abellon-Ruiz J, Killinger BJ, Rosnow JJ, Wexler AG, Folta-Stogniew E, Wright AT, van den Berg B, Goodman AL. Gut Commensal Bacteroidetes Encode a Novel Class of Vitamin B12-Binding Proteins. MBio 2022, 13: e02845-21. PMID: 35227073, PMCID: PMC8941943, DOI: 10.1128/mbio.02845-21.Peer-Reviewed Original ResearchConceptsComplex microbial communitiesHuman gut commensalTerminal globular domainModel organismsGut microbiomeMicrobial communitiesCompetitive fitnessTransport systemStructural homologsAccessory proteinsNew proteinsAdditional proteinsTransport proteinsGlobular domainUnknown functionMultiple transport systemsSystem lociKey roleGut commensalsProteinDiverse repertoireRelated moleculesMajor groupsFitnessOrganismsTuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids
Vanderschuren K, Arranz-Gibert P, Khang M, Hadar D, Gaudin A, Yang F, Folta-Stogniew E, Saltzman WM, Amiram M, Isaacs FJ. Tuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2103099119. PMID: 35046019, PMCID: PMC8794819, DOI: 10.1073/pnas.2103099119.Peer-Reviewed Original ResearchConceptsSequence-defined biopolymersProtein-based drugsModel fusion proteinProof of conceptSynthetic biopolymersBroad applicationsMaterials scienceProgrammable approachLow toxicityHigh specificityPeptide therapeuticsBiopolymersLimited side effectsConjugation sitesBlood serumBiotechnologyTechnical foundationFusion proteinMouse serumBiophysical propertiesAzidophenylalanineApplicationsPast decadeTherapeutics
2016
Homodimerization enhances both sensitivity and dynamic range of the ligand‐binding domain of type 1 metabotropic glutamate receptor
Serebryany E, Folta‐Stogniew E, Liu J, Yan EC. Homodimerization enhances both sensitivity and dynamic range of the ligand‐binding domain of type 1 metabotropic glutamate receptor. FEBS Letters 2016, 590: 4308-4317. PMID: 27800613, PMCID: PMC5154874, DOI: 10.1002/1873-3468.12473.Peer-Reviewed Original Research
2013
Oligomerization and higher‐order assembly contribute to sub‐cellular localization of a bacterial scaffold
Bowman GR, Perez AM, Ptacin JL, Ighodaro E, Folta‐Stogniew E, Comolli LR, Shapiro L. Oligomerization and higher‐order assembly contribute to sub‐cellular localization of a bacterial scaffold. Molecular Microbiology 2013, 90: 776-795. PMID: 24102805, PMCID: PMC3859194, DOI: 10.1111/mmi.12398.Peer-Reviewed Original ResearchConceptsSub-cellular localizationAmino acidsN-terminal 23 amino acidsDefective mutant proteinsAsymmetric cell divisionC-terminal 76 amino acidsC-terminal domainDimer of trimersCaulobacter crescentusCell polesLocalization determinantsHigher-order structureMutant proteinsScaffold proteinSubcellular fociCell divisionLinker domainPopZMutational analysisBiophysical analysisWild typePolar organizationOrganizing centerDistinct setsProtein
2011
Ligand-Binding Domain of Type 1 Metabotropic Glutamate Receptor is Fully Functional in iTs Monomeric Form
Serebryany E, Folta-Stogniew E, Yan E. Ligand-Binding Domain of Type 1 Metabotropic Glutamate Receptor is Fully Functional in iTs Monomeric Form. Biophysical Journal 2011, 100: 552a. DOI: 10.1016/j.bpj.2010.12.3213.Peer-Reviewed Original ResearchNucleobindin 1 is a Calcium Regulated Guanine Nucleotide Dissociation Inhibitor of GαI1
Kapoor N, Gupta R, Menon S, folta-Stogniew E, Raleigh D, Sakmar T. Nucleobindin 1 is a Calcium Regulated Guanine Nucleotide Dissociation Inhibitor of GαI1. Biophysical Journal 2011, 100: 86a. DOI: 10.1016/j.bpj.2010.12.673.Peer-Reviewed Original Research
2010
Nucleobindin 1 Is a Calcium-regulated Guanine Nucleotide Dissociation Inhibitor of Gαi1 *
Kapoor N, Gupta R, Menon ST, Folta-Stogniew E, Raleigh DP, Sakmar TP. Nucleobindin 1 Is a Calcium-regulated Guanine Nucleotide Dissociation Inhibitor of Gαi1 *. Journal Of Biological Chemistry 2010, 285: 31647-31660. PMID: 20679342, PMCID: PMC2951237, DOI: 10.1074/jbc.m110.148429.Peer-Reviewed Original ResearchConceptsNucleobindin-1Dissociation inhibitorHeterotrimeric G protein α subunitsGuanine Nucleotide Dissociation InhibitorG protein α subunitsNucleotide Dissociation InhibitorHeterotrimeric G proteinsProtein α subunitsReceptor-mediated signal transduction pathwaysSignal transduction pathwaysGoLoco motifGDI activityProtein traffickingRGS proteinsBiochemical functionsTransduction pathwaysGDP releaseΑ-subunitCalcium-binding proteinsG proteinsConformational changesBiochemical propertiesTissue culture experimentsFluorescence spectroscopy experimentsAdenylyl cyclaseQuantitative Characterization of the Interactions among c-myc Transcriptional Regulators FUSE, FBP, and FIR
Hsiao HH, Nath A, Lin CY, Folta-Stogniew EJ, Rhoades E, Braddock DT. Quantitative Characterization of the Interactions among c-myc Transcriptional Regulators FUSE, FBP, and FIR. Biochemistry 2010, 49: 4620-4634. PMID: 20420426, DOI: 10.1021/bi9021445.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCarrier ProteinsDimerizationDNA HelicasesDNA-Binding ProteinsGuanine Nucleotide Exchange FactorsHumansModels, MolecularMolecular Sequence DataNucleic Acid ConformationProtein BindingProto-Oncogene Proteins c-mycRepressor ProteinsRho Guanine Nucleotide Exchange FactorsRNA Splicing FactorsRNA-Binding ProteinsSolutionsTrans-ActivatorsConceptsDNA strand preferencesProtein-DNA interactionsC-myc transcriptionPotent oncogenic factorHuman c-mycFBP bindsTranscriptional regulationActive transcriptionNear-physiological conditionsTripartite interactionCell homeostasisInhibitory complexStrand preferenceC-MycOncogenic factorRegulatory systemUnique modeTranscriptionStrand DNABiological experimentsComplex formationLow micromolar rangeDNADifferent conformationsMicromolar range
2009
Structural Characterization of the E2 Domain of APL-1, a Caenorhabditis elegans Homolog of Human Amyloid Precursor Protein, and Its Heparin Binding Site*
Hoopes JT, Liu X, Xu X, Demeler B, Folta-Stogniew E, Li C, Ha Y. Structural Characterization of the E2 Domain of APL-1, a Caenorhabditis elegans Homolog of Human Amyloid Precursor Protein, and Its Heparin Binding Site*. Journal Of Biological Chemistry 2009, 285: 2165-2173. PMID: 19906646, PMCID: PMC2804372, DOI: 10.1074/jbc.m109.018432.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmyloid beta-Protein PrecursorAnimalsBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsCrystallography, X-RayHeparinHumansHydrogen-Ion ConcentrationMembrane ProteinsModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutationProtein StabilityProtein Structure, TertiarySequence Homology, Amino AcidSolutionsSucroseMacromolecular Interactions: Light Scattering
Folta‐Stogniew E. Macromolecular Interactions: Light Scattering. 2009 DOI: 10.1002/9780470015902.a0003143.Peer-Reviewed Original ResearchMolar massTranslational diffusion coefficientRadius of gyrationSpectroscopic techniquesAssociation stoichiometryDynamic lightBiological macromoleculesHydrodynamic radiusLight scatteringOligomeric stateStatic lightStructural studiesModified proteinsNucleic acidsSLS experimentsPhospholipid vesiclesDiffusion coefficientMacromoleculesProtein stockProteinMonodispersityDLSNanoparticlesHomoDeterminationAnalysis of the cytoplasmic interaction between polycystin-1 and polycystin-2
Casuscelli J, Schmidt S, DeGray B, Petri ET, Ćelić A, Folta-Stogniew E, Ehrlich BE, Boggon TJ. Analysis of the cytoplasmic interaction between polycystin-1 and polycystin-2. American Journal Of Physiology. Renal Physiology 2009, 297: f1310-f1315. PMID: 19726544, PMCID: PMC2781345, DOI: 10.1152/ajprenal.00412.2009.Peer-Reviewed Original Research
2008
Reexamination of the Role of the Amino Terminus of SecA in Promoting Its Dimerization and Functional State
Das S, Stivison E, Folta-Stogniew E, Oliver D. Reexamination of the Role of the Amino Terminus of SecA in Promoting Its Dimerization and Functional State. Journal Of Bacteriology 2008, 190: 7302-7307. PMID: 18723626, PMCID: PMC2580686, DOI: 10.1128/jb.00593-08.Peer-Reviewed Original ResearchConceptsWild-type SecAProtein-conducting channelCell growthAmino-terminal regionSecA dimerSecA functionsProtein translocationSecA expressionMembrane associationMutant proteinsCell fractionationATPase specific activityCorresponding proteinProtein cargoCarboxyl terminusAmino terminusVivo functionSecADimerization defectFunctional stateMutantsBiochemical studiesResidue resultsProteinChemical cross
2007
Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c‐myc inhibition
Crichlow GV, Zhou H, Hsiao HH, Frederick KB, Debrosse M, Yang Y, Folta-Stogniew EJ, Chung HJ, Fan C, De La Cruz EM, Levens D, Lolis E, Braddock D. Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c‐myc inhibition. The EMBO Journal 2007, 27: 277-289. PMID: 18059478, PMCID: PMC2206118, DOI: 10.1038/sj.emboj.7601936.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCrystallography, X-RayDimerizationDNADNA HelicasesDNA-Binding ProteinsDrosophila ProteinsGene Expression RegulationHumansMagnetic Resonance SpectroscopyMolecular Sequence DataPromoter Regions, GeneticProtein BindingProto-Oncogene Proteins c-mycRepressor ProteinsRNA Splicing FactorsRNA-Binding ProteinsTranscription Factor TFIIHConceptsRRM domainDNA bindingFirst RRM domainSecond RRM domainC-myc transcriptional controlSite-directed mutationsDNA upstreamTranscriptional controlInfluences transcriptionC-Myc inhibitionNucleic acid recognitionPromoter sitesP1 promoterAnalogous mutationCell homeostasisC-MycTFIIHProteinLight scattering revealBinding sitesDNATranscriptionSingle strandsMutationsSize exclusion chromatographyKeck Foundation Biotechnology Resource Laboratory, Yale University.
Stone KL, Bjornson RD, Blasko GG, Bruce C, Cofrancesco R, Carriero NJ, Colangelo CM, Crawford JK, Crawford JM, daSilva NC, Deluca JD, Elliott JI, Elliott MM, Flory PJ, Folta-Stogniew EJ, Gulcicek E, Kong Y, Lam TT, Lee JY, Lin A, LoPresti MB, Mane SM, McMurray WJ, Tikhonova IR, Westman S, Williams NA, Wu TL, Hongyu Z, Williams KR. Keck Foundation Biotechnology Resource Laboratory, Yale University. The Yale Journal Of Biology And Medicine 2007, 80: 195-211. PMID: 18449392, PMCID: PMC2347368.Peer-Reviewed Original ResearchThe structural basis of cyclic diguanylate signal transduction by PilZ domains
Benach J, Swaminathan SS, Tamayo R, Handelman SK, Folta‐Stogniew E, Ramos JE, Forouhar F, Neely H, Seetharaman J, Camilli A, Hunt JF. The structural basis of cyclic diguanylate signal transduction by PilZ domains. The EMBO Journal 2007, 26: 5153-5166. PMID: 18034161, PMCID: PMC2140105, DOI: 10.1038/sj.emboj.7601918.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBacterial ProteinsBinding SitesCrystallography, X-RayCyclic GMPHumansMiceModels, MolecularMolecular ConformationMolecular Sequence DataPhylogenyProtein BindingProtein Structure, QuaternaryProtein Structure, SecondaryProtein Structure, TertiarySequence AlignmentSequence Homology, Amino AcidSignal TransductionVibrio choleraeConceptsPilZ domain-containing proteinsPilZ domainDomain-containing proteinsN-terminal domainConformational switchSecond messenger cyclic diguanylateBeta-barrel foldN-terminal loopEvolutionary diversificationCyclic diguanylateSignal transductionBioinformatics analysisStructural basisInteraction surfaceSessile growthEffector pathwaysVibrio choleraeProteinV. choleraeGMPCholeraeDomainClose appositionDiguanylateEubacteria
2006
Oligomeric States of Proteins Determined by Size-Exclusion Chromatography Coupled With Light Scattering, Absorbance, and Refractive Index Detectors
Folta-Stogniew E. Oligomeric States of Proteins Determined by Size-Exclusion Chromatography Coupled With Light Scattering, Absorbance, and Refractive Index Detectors. Methods In Molecular Biology 2006, 328: 97-112. PMID: 16785643, DOI: 10.1385/1-59745-026-x:97.Peer-Reviewed Original ResearchConceptsSize exclusion chromatographyRefractive indexMolar massStatic laser lightLaser lightOligomeric stateRefractive index detectorProtein-detergent complexesLight scatteringIndex detectorUltraviolet detectionDetectorFractionation stepsNon-ionic detergentAnomalous behaviorGlycosylated proteinsChromatographyNative proteinScatteringMassPolypeptide chainStateRI analysisRI approachUniversal approach
2004
Exchange of DNA Base Pairs that Coincides with Recognition of Homology Promoted by E. coli RecA Protein
Folta-Stogniew E, O'Malley S, Gupta R, Anderson KS, Radding CM. Exchange of DNA Base Pairs that Coincides with Recognition of Homology Promoted by E. coli RecA Protein. Molecular Cell 2004, 15: 965-975. PMID: 15383285, DOI: 10.1016/j.molcel.2004.08.017.Peer-Reviewed Original ResearchConceptsE. coli RecA proteinRecognition of homologyColi RecA proteinRecA proteinBase pairsStrand exchangeSynaptic complexDouble-strand breaksT base pairsStopped-flow fluorescenceGenetic recombinationSingle strandsHomologyUnresolved mechanismDuplex DNADNA base pairsDNARate of exchangeProteinDynamic structureComplexesStrandsBasis exchangeRate of formationMechanism