1998
Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins
Kim S, Schilke B, Craig E, Horwich A. Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 12860-12865. PMID: 9789005, PMCID: PMC23633, DOI: 10.1073/pnas.95.22.12860.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCytosolEnzyme InductionHSP70 Heat-Shock ProteinsOrnithine CarbamoyltransferaseProtein BiosynthesisProtein DenaturationProtein FoldingSaccharomyces cerevisiaeConceptsOrnithine transcarbamoylaseYeast cytosolic enzymesCytosolic enzymeNative stateCytosolic Hsp70 proteinsGalpha transducinCytosolic chaperoninEukaryotic cytosolYeast Hsp70Chaperone actionPosttranslational mannerYeast cytosolCytosolic proteinsHSP70 proteinHomotrimeric enzymeProteinSpecific activity
1994
A carboxy-terminal deletion impairs the assembly of GroEL and confers a pleiotropic phenotype in Escherichia coli K-12
Burnett B, Horwich A, Low K. A carboxy-terminal deletion impairs the assembly of GroEL and confers a pleiotropic phenotype in Escherichia coli K-12. Journal Of Bacteriology 1994, 176: 6980-6985. PMID: 7961461, PMCID: PMC197070, DOI: 10.1128/jb.176.22.6980-6985.1994.Peer-Reviewed Original ResearchGroEL-mediated protein folding proceeds by multiple rounds of binding and release of nonnative forms
Weissman J, Kashi Y, Fenton W, Horwich A. GroEL-mediated protein folding proceeds by multiple rounds of binding and release of nonnative forms. Cell 1994, 78: 693-702. PMID: 7915201, DOI: 10.1016/0092-8674(94)90533-9.Peer-Reviewed Original ResearchConceptsCochaperonin GroESMultiple roundsGroEL functionChaperonin GroELKinetic partitioningMutant formsNonnative conformationsNonnative formsGroELAddition of ATPGroEL moleculeTryptophan fluorescenceFolding reactionDouble-ring structureUnfolded statePolypeptideDiverse setGroESProteolysisProteinATPBindingFateConformationComplexes
1993
Folding in vivo of bacterial cytoplasmic proteins: Role of GroEL
Horwich A, Low K, Fenton W, Hirshfield I, Furtak K. Folding in vivo of bacterial cytoplasmic proteins: Role of GroEL. Cell 1993, 74: 909-917. PMID: 8104102, DOI: 10.1016/0092-8674(93)90470-b.Peer-Reviewed Original ResearchMeSH KeywordsATP-Binding Cassette TransportersBacterial ProteinsBacteriophage lambdaCarrier ProteinsChaperonin 60Citrate (si)-SynthaseEscherichia coliEscherichia coli ProteinsHeat-Shock ProteinsKetoglutarate Dehydrogenase ComplexMaltoseMaltose-Binding ProteinsMethionineMonosaccharide Transport ProteinsOperonOrnithine CarbamoyltransferasePlasmidsPolyribonucleotide NucleotidyltransferasePromoter Regions, GeneticProtein BiosynthesisProtein FoldingProtein Sorting SignalsSequence DeletionTemperatureTransduction, GeneticConceptsCytoplasmic proteinsTemperature-sensitive lethal mutationBacterial cytoplasmic proteinsE. coli chaperonin GroELMaltose-binding proteinRole of GroELNative tertiary structureEssential genesChaperonin GroELBacterial cytoplasmMutant cellsLethal mutationsNonpermissive temperatureGenetic informationPolynucleotide phosphorylaseGeneral translationTertiary structureCitrate synthasePathways of transferKetoglutarate dehydrogenaseGeneral roleGroELNative conformationProteinTest proteins
1991
Inherited Hepatic Enzyme Defects as Candidates for Liver-Directed Gene Therapy
Horwich A. Inherited Hepatic Enzyme Defects as Candidates for Liver-Directed Gene Therapy. Current Topics In Microbiology And Immunology 1991, 168: 185-200. PMID: 1893777, DOI: 10.1007/978-3-642-76015-0_9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNAFemaleGenes, ViralGenetic TherapyHumansHydrolasesLiver DiseasesLiver TransplantationMaleMiceOrnithine CarbamoyltransferaseOrnithine Carbamoyltransferase Deficiency DiseasePrognosisTyrosine
1988
Meiotic expression of human ornithine transcarbamylase in the testes of transgenic mice.
Kelley K, Chamberlain J, Nolan J, Horwich A, Kalousek F, Eisenstadt J, Herrup K, Rosenberg L. Meiotic expression of human ornithine transcarbamylase in the testes of transgenic mice. Molecular And Cellular Biology 1988, 8: 1821-1825. PMID: 2837657, PMCID: PMC363346, DOI: 10.1128/mcb.8.4.1821.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA Restriction EnzymesGenesHumansLiverMaleMeiosisMiceMice, TransgenicNucleic Acid HybridizationOrnithine CarbamoyltransferaseRegulatory Sequences, Nucleic AcidTestisConceptsHuman ornithine transcarbamylaseFusion geneBase pairsProtein-coding sequencesMale germ cellsOrnithine transcarbamylaseMeiotic expressionRegulatory sequencesRegulatory regionsTransgenic micePachytene stageMouse metallothioneinTransgenic animalsGerm cellsGenesKilobasesTransgene expressionSequenceExpressionTranscarbamylaseMeiosisTetraploid
1987
The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge.
Horwich A, Kalousek F, Fenton W, Furtak K, Pollock R, Rosenberg L. The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge. Journal Of Cell Biology 1987, 105: 669-677. PMID: 3624306, PMCID: PMC2114782, DOI: 10.1083/jcb.105.2.669.Peer-Reviewed Original ResearchImport and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae.
Cheng M, Pollock R, Hendrick J, Horwich A. Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 4063-4067. PMID: 3295876, PMCID: PMC305022, DOI: 10.1073/pnas.84.12.4063.Peer-Reviewed Original ResearchConceptsMitochondrial membraneEnzymatic activityNH2-terminal leader peptideMitochondrial matrix fractionWild-type precursorS. cerevisiae strainMitochondrial importMammalian mitochondriaMature subunitSubunit precursorOperon promoterS. cerevisiaeSelective growth conditionsLeader peptideYeast cellsArtificial mutationsOTCase activityMatrix fractionOrnithine transcarbamoylaseCerevisiae strainSaccharomycesGrowth conditionsMatrix compartmentMitochondriaSubunits
1986
Targeting of Nuclear‐Encoded Proteins to the Mitochondrial Matrix: Implications for Human Genetic Defects
ROSENBERG L, FENTON W, HORWICH A, KALOUSEK F, KRAUS J. Targeting of Nuclear‐Encoded Proteins to the Mitochondrial Matrix: Implications for Human Genetic Defects. Annals Of The New York Academy Of Sciences 1986, 488: 99-108. PMID: 3472484, DOI: 10.1111/j.1749-6632.1986.tb54396.x.Peer-Reviewed Original ResearchDNA analysis for ornithine transcarbamylase deficiency
Rozen R, Fox J, Hack A, Fenton W, Horwich A, Rosenberg L. DNA analysis for ornithine transcarbamylase deficiency. Journal Of Inherited Metabolic Disease 1986, 9: 49-57. PMID: 2878115, DOI: 10.1007/bf01800858.Peer-Reviewed Original ResearchTargeting of pre-ornithine transcarbamylase to mitochondria: Definition of critical regions and residues in the leader peptide
Horwich A, Kalousek F, Fenton W, Pollock R, Rosenberg L. Targeting of pre-ornithine transcarbamylase to mitochondria: Definition of critical regions and residues in the leader peptide. Cell 1986, 44: 451-459. PMID: 3943133, DOI: 10.1016/0092-8674(86)90466-6.Peer-Reviewed Original ResearchArginineEnzyme PrecursorsMitochondriaMutationOrnithine CarbamoyltransferaseProtein ConformationProtein Sorting Signals
1985
Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor.
Horwich A, Kalousek F, Rosenberg L. Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1985, 82: 4930-4933. PMID: 3895227, PMCID: PMC390471, DOI: 10.1073/pnas.82.15.4930.Peer-Reviewed Original ResearchConceptsLeader peptideOrnithine transcarbamoylaseImport of precursorsMost mitochondrial proteinsMitochondrial matrix fractionOverall amino acid compositionMitochondrial matrix enzymeMitochondrial precursorsMitochondrial proteinsSubunit precursorAmino acid compositionBasic arginine residuesBasic residuesMatrix enzymeGlycine residueLarger precursorArginine residuesMatrix fractionIntact mitochondriaNH2-terminalDependent proteaseProteolytic cleavageTranscarbamoylaseResiduesMitochondriaExpression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor.
Horwich A, Fenton W, Firgaira F, Fox J, Kolansky D, Mellman I, Rosenberg L. Expression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor. Journal Of Cell Biology 1985, 100: 1515-1521. PMID: 3988798, PMCID: PMC2113848, DOI: 10.1083/jcb.100.5.1515.Peer-Reviewed Original ResearchConceptsMitochondrial importOTC precursorsHeLa cellsOrnithine transcarbamylaseArginine residuesMouse dihydrofolate reductaseNH2-terminal leader sequenceRate of importArginine analog canavanineViral regulatory elementsImmunoprecipitation of extractsMitochondrial localizationCDNA sequenceRegulatory elementsLeader sequenceDNA sequencesEnzyme precursorsMitochondrial enzymesCell extractsDihydrofolate reductaseEnzymatic activityBlot analysisNormal precursorsResiduesSubunitsA leader peptide is sufficient to direct mitochondrial import of a chimeric protein.
Horwich A, Kalousek F, Mellman I, Rosenberg L. A leader peptide is sufficient to direct mitochondrial import of a chimeric protein. The EMBO Journal 1985, 4: 1129-1135. PMID: 3891325, PMCID: PMC554314, DOI: 10.1002/j.1460-2075.1985.tb03750.x.Peer-Reviewed Original ResearchConceptsChimeric precursor proteinsMitochondrial importLeader peptideChimeric precursorsDihydrofolate reductaseMost mitochondrial proteinsPost-translational importMutant CHO cell linesCloned nucleotide sequencePrecursor proteinOrnithine transcarbamylaseCell-free systemCHO cell linesEnzyme dihydrofolate reductaseMitochondrial proteinsMitochondrial localizationRegulatory elementsLeader sequenceNucleotide sequenceStable transformantsAdditional proteinsSelectable markerChimeric proteinLarger precursorIntact cellsA cDNA clone for the precursor of rat mitochondrial ornithine transcarbamylase: comparison of rat and human leader sequences and conservation of catalytic sites
Kraus J, Hodges P, Williamson C, Horwich A, Kalousek F, Williams K, Rosenberg L. A cDNA clone for the precursor of rat mitochondrial ornithine transcarbamylase: comparison of rat and human leader sequences and conservation of catalytic sites. Nucleic Acids Research 1985, 13: 943-952. PMID: 3839075, PMCID: PMC341044, DOI: 10.1093/nar/13.3.943.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesDNAEnzyme PrecursorsHumansMitochondria, LiverOrnithine CarbamoyltransferaseRatsRNA, MessengerConceptsAmino acid sequenceLeader sequenceAcid sequenceBasic residuesAmino-terminal leader sequenceE. coliComplete sequence homologyAmino acid residuesProtein sequence dataOrnithine transcarbamylaseCDNA clonesSequence dataDNA complementaryOrnithine transcarbamylasesSequence homologyEntire proteinHuman enzymeAcid residuesTranscarbamylasesComplementary DNAAmino acidsMessenger RNARat enzymeNucleotidesCatalytic siteGene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus
Rozen R, Fox J, Fenton W, Horwich A, Rosenberg L. Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus. Nature 1985, 313: 815-817. PMID: 2983225, DOI: 10.1038/313815a0.Peer-Reviewed Original Research
1984
Human Ornithine Transcarbamylase Locus Mapped to Band Xp21.1 Near the Duchenne Muscular Dystrophy Locus
Lindgren V, de Martinville B, Horwich A, Rosenberg L, Francke U. Human Ornithine Transcarbamylase Locus Mapped to Band Xp21.1 Near the Duchenne Muscular Dystrophy Locus. Science 1984, 226: 698-700. PMID: 6494904, DOI: 10.1126/science.6494904.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromosome MappingDNAFemaleHumansMaleMiceMuscular DystrophiesNucleic Acid HybridizationOrnithine CarbamoyltransferasePrenatal DiagnosisSex Chromosome AberrationsX ChromosomeConceptsMitochondrial enzyme ornithine transcarbamylaseHuman ornithine transcarbamylase geneSitu hybridization experimentsOrnithine transcarbamylase geneGene mapsX chromosomeHybridization experimentsDuchenne muscular dystrophy locusShort armGenesX chromosome abnormalitiesMuscular dystrophyCell linesOrnithine transcarbamylaseLociChromosome abnormalitiesCarrier detectionChromosomesDuchenne muscular dystrophyXp21.1DNATranscarbamylaseProbeDystrophyOrnithine transcarbamylase deficiencyStructure and Expression of a Complementary DNA for the Nuclear Coded Precursor of Human Mitochondrial Ornithine Transcarbamylase
Horwich A, Fenton W, Williams K, Kalousek F, Kraus J, Doolittle R, Konigsberg W, Rosenberg L. Structure and Expression of a Complementary DNA for the Nuclear Coded Precursor of Human Mitochondrial Ornithine Transcarbamylase. Science 1984, 224: 1068-1074. PMID: 6372096, DOI: 10.1126/science.6372096.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCloning, MolecularDNADNA, MitochondrialDNA, RecombinantEscherichia coliHeLa CellsHumansMitochondriaOrnithine CarbamoyltransferaseProtein BiosynthesisRatsConceptsComplementary DNALeader peptideOrnithine transcarbamylaseAmino-terminal leader peptideMost mitochondrial proteinsComplete primary structureHuman ornithine transcarbamylaseFree cytoplasmic ribosomesMitochondrial matrix enzymeCultured HeLa cellsMitochondrial proteinsCytoplasmic ribosomesRegulatory elementsNucleotide sequenceStable transformantsMatrix enzymeAsparagine residuesAcidic residuesLarger precursorMature formPrimary structureProtein occursHeLa cellsEscherichia coliAmino acids
1983
Molecular cloning of the cDNA coding for rat ornithine transcarbamoylase.
Horwich A, Kraus J, Williams K, Kalousek F, Konigsberg W, Rosenberg L. Molecular cloning of the cDNA coding for rat ornithine transcarbamoylase. Proceedings Of The National Academy Of Sciences Of The United States Of America 1983, 80: 4258-4262. PMID: 6576335, PMCID: PMC384016, DOI: 10.1073/pnas.80.14.4258.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCloning, MolecularDNAGenesLiverNucleic Acid HybridizationOrnithine CarbamoyltransferasePlasmidsProtein BiosynthesisRatsRNA, MessengerConceptsOrnithine transcarbamoylaseSequential Edman analysesCDNA probeMitochondrial matrix enzymeInsertion of cDNAAmino acid residuesConsecutive amino acid residuesCarboxyl-terminal portionCytoplasmic polysomesMolecular cloningCDNA clonesEdman analysisDifferential colony hybridizationTranslation assaysX chromosomeCDNA codingMatrix enzymeEnzyme subunitMessenger speciesAcid residuesSequence presentPolysome immunoadsorptionIdentical subunitsColony hybridizationEscherichia coli