2023
Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression
Jiang H, Ambrose N, Chung C, Wang Y, Söll D, Tharp J. Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2219758120. PMID: 36787361, PMCID: PMC9974479, DOI: 10.1073/pnas.2219758120.Peer-Reviewed Original ResearchConceptsAminoacyl-tRNA synthetasesCodon suppressionStop codon suppressionGene expressionOrthogonal aminoacyl-tRNA synthetasesRelevant protein-protein interactionsSynthetic biology toolsSmall molecule rapamycinControl gene expressionProtein-protein interactionsLevel of transcriptionAbscisic acidDimerization domainMammalian cellsBiology toolsGene translationTranslational levelMolecular switchStop codonHuman cellsMolecular inputsUseful biotechnologySynthetasesExpressionTherapeutic applications
2022
Measuring the tolerance of the genetic code to altered codon size
DeBenedictis EA, Söll D, Esvelt KM. Measuring the tolerance of the genetic code to altered codon size. ELife 2022, 11: e76941. PMID: 35293861, PMCID: PMC9094753, DOI: 10.7554/elife.76941.Peer-Reviewed Original ResearchConceptsFour-base codonsGenetic codeTRNA mutationsAminoacyl-tRNA synthetasesQuadruplet codonsSingle amino acidCodon translationTriplet codonsTRNA synthetasesSynthetic biologistsCodonTRNAAmino acidsChemical alphabetsMutationsMass spectrometrySynthetasesAnticodonToleranceSynthetic systemsBiologistsTranslationEscherichiaNascent
2014
Exploring the Substrate Range of Wild‐Type Aminoacyl‐tRNA Synthetases
Fan C, Ho JM, Chirathivat N, Söll D, Wang Y. Exploring the Substrate Range of Wild‐Type Aminoacyl‐tRNA Synthetases. ChemBioChem 2014, 15: 1805-1809. PMID: 24890918, PMCID: PMC4133344, DOI: 10.1002/cbic.201402083.Peer-Reviewed Original ResearchConceptsAminoacyl-tRNA synthetasesSubstrate rangeDifferent amino acid sitesAmino acidsE. coli tryptophanyl-tRNA synthetaseE. coli aminoacyl-tRNA synthetasesAmino acid sitesCanonical amino acidsNonstandard amino acidsTyrosyl-tRNA synthetaseTryptophanyl-tRNA synthetaseAnticodon sequenceTRNA synthetasesSynthetasesSynthetaseSequenceAnticodonNSAAsTrpRSProteinAminoacylAcid
2012
The Mechanism of Pre-transfer Editing in Yeast Mitochondrial Threonyl-tRNA Synthetase*
Ling J, Peterson KM, Simonović I, Söll D, Simonović M. The Mechanism of Pre-transfer Editing in Yeast Mitochondrial Threonyl-tRNA Synthetase*. Journal Of Biological Chemistry 2012, 287: 28518-28525. PMID: 22773845, PMCID: PMC3436575, DOI: 10.1074/jbc.m112.372920.Peer-Reviewed Original ResearchConceptsPre-transfer editingThreonyl-tRNA synthetaseHydrolytic water moleculeFundamental biological processesNormal cellular functionAminoacyl-tRNA synthetasesPost-transfer editingPost-transfer editing activityTranslational fidelityAminoacylation siteCellular functionsAminoacylation active siteBiological processesMST1Conformational changesEditing activitySeryl adenylateAmino acidsSpecialized domainsEditingSerineSites 100SynthetaseActive siteAdenylateYeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment
Ling J, Peterson KM, Simonović I, Cho C, Söll D, Simonović M. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3281-3286. PMID: 22343532, PMCID: PMC3295322, DOI: 10.1073/pnas.1200109109.Peer-Reviewed Original ResearchMeSH KeywordsAeropyrumAmino Acid SequenceAnticodonCatalytic DomainCodonCrystallography, X-RayEscherichia coliEvolution, MolecularLeucineMitochondriaModels, MolecularMolecular Sequence DataProtein ConformationProtein Structure, TertiaryRNA EditingRNA, Transfer, Amino AcylSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSpecies SpecificityStaphylococcus aureusSubstrate SpecificityThreonineThreonine-tRNA LigaseConceptsThreonyl-tRNA synthetaseAnticodon loopAnticodon sequenceEscherichia coli ThrRSSet of tRNAsDistinct recognition mechanismsAnticodon-binding domainAminoacyl-tRNA synthetasesCUN codonsDetailed structural comparisonCodon reassignmentYeast mitochondriaGenetic codeTRNA isoacceptorsSaccharomyces cerevisiaeIsoacceptor tRNAsEditing domainTRNAMST1Anticodon tripletStructural comparisonNatural tRNAAmino acidsDistinct mechanismsRecognition mechanism
2011
Rational design of an evolutionary precursor of glutaminyl-tRNA synthetase
O’Donoghue P, Sheppard K, Nureki O, Söll D. Rational design of an evolutionary precursor of glutaminyl-tRNA synthetase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20485-20490. PMID: 22158897, PMCID: PMC3251134, DOI: 10.1073/pnas.1117294108.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acyl-tRNA SynthetasesBase SequenceCodonEscherichia coliEvolution, MolecularGenetic EngineeringKineticsMethanobacteriaceaeModels, MolecularMolecular ConformationMolecular Sequence DataNucleic Acid ConformationPhylogenyProtein Structure, SecondarySequence Homology, Amino AcidConceptsGlutaminyl-tRNA synthetaseAminoacyl-tRNA synthetasesGenetic code engineeringAmino acidsDomains of lifeMost aminoacyl-tRNA synthetasesGlutamyl-tRNA synthetaseCanonical amino acidsBacterial GlnRSTRNA specificityTRNA pairsParticular codonsEvolutionary precursorBiochemical characterizationStem loopGlnRAdditional codonsCAA codonCodonProtein synthesisCAG codonEscherichia coliSpecific enzymesCatalytic preferenceSynthetase
2008
Quality control despite mistranslation caused by an ambiguous genetic code
Ruan B, Palioura S, Sabina J, Marvin-Guy L, Kochhar S, LaRossa RA, Söll D. Quality control despite mistranslation caused by an ambiguous genetic code. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 16502-16507. PMID: 18946032, PMCID: PMC2575449, DOI: 10.1073/pnas.0809179105.Peer-Reviewed Original ResearchConceptsGenetic codeAa-tRNAWild-type proteinAminoacyl-tRNA synthetasesInactive mutant proteinsHeat shock responseE. coliMutant proteinsReporter proteinMissense suppressionFunctional proteinsCognate tRNASelective pressureAminoacyl-tRNAActive enzymeShock responseProtein synthesisNative conformationEnergetic costAmino acidsMissense mutationsProteinBiochemical evidenceCorrect pairingProtein quality
2007
Features of Aminoacyl‐tRNA Synthesis Unique to Archaea
Polycarpo C, Sheppard K, Randau L, Ambrogelly A, Cardoso A, Fukai S, Herring S, Hohn M, Nakamura Y, Oshikane H, Palioura S, Salazar J, Yuan J, Nureki O, Söll D. Features of Aminoacyl‐tRNA Synthesis Unique to Archaea. 2007, 198-208. DOI: 10.1128/9781555815516.ch9.Peer-Reviewed Original ResearchAminoacyl-tRNA synthetasesAmino acidsCognate tRNA speciesCorrect amino acidDomains of lifeAminoacyl-tRNA synthetaseIntron-exon junctionsCorresponding tRNAsNanoarchaeum equitansMethylated thiolsM. jannaschiiMature tRNATRNA speciesGenomic studiesAncient familyBulge motifCysteine synthesisMethanogenic archaeaArchaeaBiosynthetic routeAa-tRNATRNATwo-step pathwayCys-tRNACysSynthetases
2006
Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrion
Krett B, Rinehart J, Rubio M, Alfonzo J, Söll D. Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrion. The FASEB Journal 2006, 20: a500-a500. DOI: 10.1096/fasebj.20.4.a500-b.Peer-Reviewed Original ResearchTransamidation pathwayMitochondrial translationGln-tRNAOrganellar protein synthesisYeast mitochondrial DNAGlutaminyl-tRNA synthetaseAminoacyl-tRNA synthetasesAminoacyl-tRNA formationImport mechanismMitochondrial localizationMitochondrial DNAProtein biosynthesisMost bacteriaCytoplasmic componentsAlternate functionsCytosolic pathwayProtein synthesisAmino acidsEssential processMitochondriaTRNAPathwayEukaryotesGlnRArchaea
2004
Cys-tRNACys formation and cysteine biosynthesis in methanogenic archaea: two faces of the same problem?
Ambrogelly A, Kamtekar S, Sauerwald A, Ruan B, Tumbula-Hansen D, Kennedy D, Ahel I, Söll D. Cys-tRNACys formation and cysteine biosynthesis in methanogenic archaea: two faces of the same problem? Cellular And Molecular Life Sciences 2004, 61: 2437-2445. PMID: 15526152, DOI: 10.1007/s00018-004-4194-9.Peer-Reviewed Original ResearchConceptsMethanogenic archaeaCysteine biosynthesisCellular translation machineryAminoacyl-tRNA synthesisCanonical cysteinyl-tRNA synthetaseAminoacyl-tRNA synthetasesCysteinyl-tRNA synthetaseRecognizable genesTranslation machineryGenome sequenceArchaeaBiosynthesisEssential componentSynthetasesTRNARibosomesGenesMachineryOrganismsSynthetasePossible linkSequenceFormation
2003
Non-canonical Eukaryotic Glutaminyl- and Glutamyl-tRNA Synthetases Form Mitochondrial Aminoacyl-tRNA in Trypanosoma brucei *
Rinehart J, Horn EK, Wei D, Söll D, Schneider A. Non-canonical Eukaryotic Glutaminyl- and Glutamyl-tRNA Synthetases Form Mitochondrial Aminoacyl-tRNA in Trypanosoma brucei *. Journal Of Biological Chemistry 2003, 279: 1161-1166. PMID: 14563839, DOI: 10.1074/jbc.m310100200.Peer-Reviewed Original ResearchConceptsGlutaminyl-tRNA synthetaseGlutamyl-tRNA synthetaseT. bruceiGln-tRNATrypanosoma bruceiInsect stage T. bruceiT. brucei enzymeRespective gene productsAminoacyl-tRNA synthetasesGlutamyl-tRNA synthetase activitySynthetase activityTransamidation pathwayLeishmania mitochondriaBrucei enzymeMitochondrial tRNAsGlu-tRNAProtein biosynthesisAminoacylation experimentsGene productsRNA interferenceTRNABruceiMitochondriaTotal tRNAGlutaminyl
2002
tRNA‐dependent amino acid discrimination by yeast seryl‐tRNA synthetase
Gruic‐Sovulj I, Landeka I, Söll D, Weygand‐Durasevic I. tRNA‐dependent amino acid discrimination by yeast seryl‐tRNA synthetase. The FEBS Journal 2002, 269: 5271-5279. PMID: 12392560, DOI: 10.1046/j.1432-1033.2002.03241.x.Peer-Reviewed Original ResearchConceptsSeryl-tRNA synthetaseYeast seryl-tRNA synthetaseCognate tRNA moleculesAmino acid discriminationAminoacyl-tRNA synthetasesAmino acid substratesSimilar amino acidsAmino acid serineGenetic codeEnzyme active siteTRNA moleculesActive siteYeast SerRSConformational changesAcid substratesAmino acidsSerineSynthetaseStoichiometric analysisDifferent affinitiesEnzymeAccurate translationTRNASerSynthetasesSaccharomyces
2001
Cysteinyl-tRNA synthetase is not essential for viability of the archaeon Methanococcus maripaludis
Stathopoulos C, Kim W, Li T, Anderson I, Deutsch B, Palioura S, Whitman W, Söll D. Cysteinyl-tRNA synthetase is not essential for viability of the archaeon Methanococcus maripaludis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 14292-14297. PMID: 11717392, PMCID: PMC64675, DOI: 10.1073/pnas.201540498.Peer-Reviewed Original ResearchConceptsCysteinyl-tRNA synthetaseMethanococcus maripaludisArchaeon Methanococcus maripaludisLateral gene transferNormal growth conditionsAminoacyl-tRNA synthetasesAminoacyl-tRNA synthetaseArchaea Methanocaldococcus jannaschiiProlyl-tRNA synthetaseCysS genesCys-tRNAMethanocaldococcus jannaschiiM. maripaludisSynthetase geneIntriguing enzymeMethanothermobacter thermautotrophicusCysteinyl-tRNAKnockout strainProlyl-tRNAGene transferSynthetaseBiochemical analysisVivo translationGrowth conditionsCysRSA Single Amidotransferase Forms Asparaginyl-tRNA and Glutaminyl-tRNA in Chlamydia trachomatis *
Raczniak G, Becker H, Min B, Söll D. A Single Amidotransferase Forms Asparaginyl-tRNA and Glutaminyl-tRNA in Chlamydia trachomatis *. Journal Of Biological Chemistry 2001, 276: 45862-45867. PMID: 11585842, DOI: 10.1074/jbc.m109494200.Peer-Reviewed Original ResearchConceptsAsn-tRNAGln-tRNAAminoacyl-tRNAOperon-like arrangementAccurate protein synthesisGlutaminyl-tRNA synthetaseGlutamyl-tRNA synthetaseAminoacyl-tRNA synthetasesAsparaginyl-tRNA synthetaseAspartyl-tRNA synthetaseGat genesAsparaginyl-tRNAGenome sequenceMost bacteriaGlutaminyl-tRNAAmidotransferaseProtein synthesisSynthetasesSynthetaseGenesAmide donorEnzymeAspGluGenomeGenomics and the evolution of aminoacyl-tRNA synthesis.
Ruan B, Ahel I, Ambrogelly A, Becker H, Bunjun S, Feng L, Tumbula-Hansen D, Ibba M, Korencic D, Kobayashi H, Jacquin-Becker C, Mejlhede N, Min B, Raczniak G, Rinehart J, Stathopoulos C, Li T, Söll D. Genomics and the evolution of aminoacyl-tRNA synthesis. Acta Biochimica Polonica 2001, 48: 313-21. PMID: 11732603, DOI: 10.18388/abp.2001_3917.Peer-Reviewed Original ResearchConceptsAminoacyl-tRNA synthesisAminoacyl-tRNA synthetasesTransfer RNAsAmino acidsMessenger RNAGenetic informationContemporary aminoacyl-tRNA synthetasesDirect protein synthesisNon-canonical routesEvolutionary diversityEvolutionary divergenceCys-tRNANascent polypeptidesRibosome movesAsn-tRNAGln-tRNAWhole genomeAppropriate amino acidsTRNA anticodonSubstrate specificityLys-tRNATrinucleotide codonsNext codonUnexpected levelProtein synthesis
2000
Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process
Woese C, Olsen G, Ibba M, Söll D. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process. Microbiology And Molecular Biology Reviews 2000, 64: 202-236. PMID: 10704480, PMCID: PMC98992, DOI: 10.1128/mmbr.64.1.202-236.2000.Peer-Reviewed Original ResearchConceptsAminoacyl-tRNA synthetasesIndividual aminoacyl-tRNA synthetasesEvolutionary processesAAR geneEvolutionary relationshipsPhylogenetic treeGenetic codeUniversal phylogenetic treeDistant evolutionary pastOrganismal phylogenyOrganismal domainsCodon assignmentsTaxonomic distributionEvolutionary pastHorizontal transferEvolutionary profilesGenetic materialIndividual enzymesEvolutionary perspectiveSynthetasesGenesEnzymeBacteriaModern counterpartsTreesTransfer RNA Identity Change in Anticodon Variants of E. coli tRNAPhe in Vivo
Kim H, Kim I, Söll D, Lee Y. Transfer RNA Identity Change in Anticodon Variants of E. coli tRNAPhe in Vivo. Molecules And Cells 2000, 10: 76-82. PMID: 10774751, DOI: 10.1007/s10059-000-0076-7.Peer-Reviewed Original ResearchConceptsMutant tRNA genesMutant tRNAsTRNA genesAnticodon sequenceAnticodon mutantsHost viabilityE. coliAmino acidsMost aminoacyl-tRNA synthetasesOpal stop codonAminoacyl-tRNA synthetasesSite-directed mutagenesisE. coli tRNAMajor recognition elementAnticodon variantsSuch tRNAsTRNAStop codonAminoacylation specificityAnticodonSimilarity dendrogramVivo evolutionGenesAcceptor specificityAnticodon change
1999
Substrate recognition by class I lysyl-tRNA synthetases: A molecular basis for gene displacement
Ibba M, Losey H, Kawarabayasi Y, Kikuchi H, Bunjun S, Söll D. Substrate recognition by class I lysyl-tRNA synthetases: A molecular basis for gene displacement. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 418-423. PMID: 9892648, PMCID: PMC15151, DOI: 10.1073/pnas.96.2.418.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesBase SequenceBorrelia burgdorferi GroupCloning, MolecularDiphosphatesEscherichia coliEvolution, MolecularGenes, ArchaealGenes, BacterialGenetic Complementation TestKineticsLysine-tRNA LigaseMethanococcusMolecular Sequence DataNucleic Acid ConformationPhylogenyRNA, Transfer, Amino AcylSequence Analysis, DNASubstrate SpecificityTranscription, GeneticConceptsClass II LysRSAminoacyl-tRNA synthetasesLysyl-tRNA synthetasesSubstrate recognitionMolecular basisBacterial class IClass II enzymesSequence-specific recognitionGene displacementTranslational apparatusTRNA recognitionEscherichia coli strainsLysRSLysRSsSame nucleotideSynthetasesDiscriminator baseUnrelated typesLysine activationCertain bacteriaII enzymesColi strainsTRNALysClass IEnzyme
1997
Archaeal-type lysyl-tRNA synthetase in the Lyme disease spirochete Borrelia burgdorferi
Ibba M, Bono J, Rosa P, Söll D. Archaeal-type lysyl-tRNA synthetase in the Lyme disease spirochete Borrelia burgdorferi. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 14383-14388. PMID: 9405621, PMCID: PMC24988, DOI: 10.1073/pnas.94.26.14383.Peer-Reviewed Original ResearchConceptsLysyl-tRNA synthetasesLysyl-tRNA synthetaseOpen reading frameReading frameAminoacyl-tRNA synthetasesLyme disease spirochete Borrelia burgdorferiGroup of enzymesLysyl-tRNA synthetase activityAmino acid levelsBacterial pathogen Borrelia burgdorferiArchaeal kingdomHeterologous expressionProtein biosynthesisGenomic sequencesMRNA translationPathogen Borrelia burgdorferiSignificant similarityLysyl-tRNASynthetasesB. burgdorferiBorrelia burgdorferiEscherichia coliEukaryaSpirochete Borrelia burgdorferiPathogenic spirochetesA Euryarchaeal Lysyl-tRNA Synthetase: Resemblance to Class I Synthetases
Ibba M, Morgan S, Curnow A, Pridmore D, Vothknecht U, Gardner W, Lin W, Woese C, Söll D. A Euryarchaeal Lysyl-tRNA Synthetase: Resemblance to Class I Synthetases. Science 1997, 278: 1119-1122. PMID: 9353192, DOI: 10.1126/science.278.5340.1119.Peer-Reviewed Original ResearchConceptsClass I aminoacyl-tRNA synthetaseCrenarchaeote Sulfolobus solfataricusDinucleotide-binding domainAminoacyl-tRNA synthetasesAmino acid motifsAmino acid sequenceAminoacyl-tRNA synthetaseLysyl-tRNA synthetaseClass II synthetasesEuryarchaeal genomesUnassigned functionMethanococcus jannaschiiMethanococcus maripaludisLysRS proteinsReading frameSulfolobus solfataricusAcid motifAcid sequenceSuch organismsMethanobacterium thermoautotrophicumLysRSProteinSynthetasesSynthetaseRNA synthetase