2023
Mapping the in vivo fitness landscape of a tethered ribosome
Radford F, Rinehart J, Isaacs F. Mapping the in vivo fitness landscape of a tethered ribosome. Science Advances 2023, 9: eade8934. PMID: 37115918, PMCID: PMC10146877, DOI: 10.1126/sciadv.ade8934.Peer-Reviewed Original ResearchConceptsPeptidyl transfer centerEpistatic interactionsFitness landscapeMacromolecular machinesLaboratory evolutionRibosome functionDeleterious mutationsVivo fitness landscapeComplete mutagenesisLethal mutationsGenetic elementsRibosomesProtein synthesisDominant lethal mutationsMost nucleotidesMutationsSequence spaceNucleotidesNext-generation biomaterialsLandscapeMutagenesisOrganismsSequenceInteractionDeeper understanding
2020
The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporation
Han N, Bullwinkle T, Loeb K, Faull K, Mohler K, Rinehart J, Ibba M. The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporation. Journal Of Biological Chemistry 2020, 295: 1402-1410. DOI: 10.1016/s0021-9258(17)49898-x.Peer-Reviewed Original ResearchAmino acid activationSerine codonsProtein synthesisHuman protein extractsHuman seryl-tRNA synthetaseAminoacyl-tRNA synthetaseSeryl-tRNA synthetaseAmyotrophic lateral sclerosisAlanyl-tRNA synthetaseN-methylaminoNonproteinogenic amino acidsCotranslational incorporationTRNA aminoacylationAlzheimer's diseaseProtein extractsBiochemical assaysAmino acidsExchange assayBMAAAcid activationSynthetaseCodonAminoacylationNeurodegenerative diseasesMultiple different mechanisms
2015
Robust production of recombinant phosphoproteins using cell-free protein synthesis
Oza JP, Aerni HR, Pirman NL, Barber KW, ter Haar CM, Rogulina S, Amrofell MB, Isaacs FJ, Rinehart J, Jewett MC. Robust production of recombinant phosphoproteins using cell-free protein synthesis. Nature Communications 2015, 6: 8168. PMID: 26350765, PMCID: PMC4566161, DOI: 10.1038/ncomms9168.Peer-Reviewed Original ResearchConceptsMEK1 activityMultiple phosphorylated residuesCo-translational incorporationSite-specific protein phosphorylationCell-free protein synthesis platformHigh-throughput technology platformsCell-free protein synthesisSite-specific phosphorylationStructure-function relationshipsRecombinant phosphoproteinsPhosphorylation eventsMEK1 kinasePhosphorylated residuesProtein phosphorylationProtein synthesisEscherichia coliPhosphoproteinRobust productionSynthesis platformStructural consequencesDirect expressionPhosphorylationTechnology platformKinasePhosphoserine
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
2001
Genomics 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