Featured Publications
A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery
Marcotrigiano J, Lomakin I, Sonenberg N, Pestova T, Hellen C, Burley S. A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery. Molecular Cell 2001, 7: 193-203. PMID: 11172724, DOI: 10.1016/s1097-2765(01)00167-8.Peer-Reviewed Original ResearchConceptsInternal ribosome entry siteTranslation initiation machineryInitiation machineryHEAT domainATP-dependent RNA helicase eIF4AStructure-based site-directed mutagenesisCap-independent translation initiationRNA helicase eIF4ASite-directed mutagenesisPicornaviral internal ribosome-entry siteRibosome entry siteRibosomal complex formationHelicase eIF4ATranslation initiationAlpha-helixEntry siteEIF4AMechanistic insightsX-ray structureComplex formationMachineryBiochemical resultsEssential componentDomainMutagenesisMolecular mechanisms of translation initiation in eukaryotes
Pestova T, Kolupaeva V, Lomakin I, Pilipenko E, Shatsky I, Agol V, Hellen C. Molecular mechanisms of translation initiation in eukaryotes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 7029-7036. PMID: 11416183, PMCID: PMC34618, DOI: 10.1073/pnas.111145798.Peer-Reviewed Original ResearchThe fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH
Lomakin IB, Shirokikh NE, Yusupov MM, Hellen C, Pestova TV. The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH. The EMBO Journal 2005, 25: 196-210. PMID: 16362046, PMCID: PMC1356347, DOI: 10.1038/sj.emboj.7600904.Peer-Reviewed Original ResearchConceptsInitiator tRNA selectionRibosomal subunitTRNA selectionEukaryotic initiation factors eIF1Common evolutionary originSmall ribosomal subunitInitiation factor eIF1Initiation factor IF3Initiation codon selectionCodon-anticodon mismatchesEIF2-bound GTPRelated conformational changesIF3 functionEvolutionary originSmall ribosomalTranslation initiationInitiation complexInitiation factorsFactor bindingInitiation codonTerminal domainHeterologous systemsCodon selectionInitiator tRNAHeterologous subunitsThe joining of ribosomal subunits in eukaryotes requires eIF5B
Pestova T, Lomakin I, Lee J, Choi S, Dever T, Hellen C. The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature 2000, 403: 332-335. PMID: 10659855, DOI: 10.1038/35002118.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCatalysisCodon, InitiatorEukaryotic Initiation Factor-1Eukaryotic Initiation Factor-2Eukaryotic Initiation Factor-3Eukaryotic Initiation Factor-5GTP PhosphohydrolasesGuanosine TriphosphateGuanylyl ImidodiphosphateHumansHydrolysisMolecular Sequence DataPeptide Chain Initiation, TranslationalPeptide Initiation FactorsPuromycinRecombinant ProteinsRibosomesRNA, MessengerConceptsEIF2-bound GTPEukaryotic initiation factor 3RNA ternary complexRibosome-dependent GTPase activityInitiation factor IF2Initiation factor 3Eukaryotic protein synthesisRibosomal subunitInitiation codonGTPase activityProtein synthesisMessenger RNASubunitsTernary complexFactor 3GTPComplexesEukaryotesEIF5EIF5BEIF2EIF4BEIF1ARibosomesIF2
2016
Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition
Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Research 2016, 44: 2439-2450. PMID: 26809677, PMCID: PMC4797290, DOI: 10.1093/nar/gkw018.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBinding SitesCattleCrystallography, X-RayEscherichia coliInsect ProteinsModels, MolecularMolecular Sequence DataPeptides, CyclicProtein BindingProtein BiosynthesisRibosomesRNA, MessengerRNA, TransferSpecies SpecificityThermus thermophilus
2004
Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly
Pestova TV, Lomakin IB, Hellen CU. Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly. EMBO Reports 2004, 5: 906-913. PMID: 15332113, PMCID: PMC1299141, DOI: 10.1038/sj.embor.7400240.Peer-Reviewed Original Research
2003
Transcript cleavage factors GreA and GreB act as transient catalytic components of RNA polymerase
Laptenko O, Lee J, Lomakin I, Borukhov S. Transcript cleavage factors GreA and GreB act as transient catalytic components of RNA polymerase. The EMBO Journal 2003, 22: 6322-6334. PMID: 14633991, PMCID: PMC291851, DOI: 10.1093/emboj/cdg610.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCatalysisCross-Linking ReagentsDNA-Directed RNA PolymerasesEndoribonucleasesEscherichia coliEscherichia coli ProteinsHydroxyl RadicalModels, MolecularMolecular Sequence DataProtein ConformationProtein SubunitsSequence AlignmentSequence Homology, Amino AcidTranscription FactorsTranscription, GeneticTranscriptional Elongation FactorsConceptsN-terminal coiled-coil domainRNA polymeraseTranscription elongation factors GreANucleolytic activityRNAP secondary channelFirst transcription factorRNA hydrolysisRNAP catalytic centerCoiled-coil domainMolecular genetic methodsTerminal globular domainTranscription elongationTranscriptional pausingTranscription initiationTranscription factorsGenetic methodsKey residuesBiological roleGlobular domainCatalytic componentCatalytic centerGreAPolymeraseCatalytic actSecondary channelEukaryotic Initiation Factors 4G and 4A Mediate Conformational Changes Downstream of the Initiation Codon of the Encephalomyocarditis Virus Internal Ribosomal Entry Site
Kolupaeva VG, Lomakin IB, Pestova TV, Hellen CU. Eukaryotic Initiation Factors 4G and 4A Mediate Conformational Changes Downstream of the Initiation Codon of the Encephalomyocarditis Virus Internal Ribosomal Entry Site. Molecular And Cellular Biology 2003, 23: 687-698. PMID: 12509466, PMCID: PMC151537, DOI: 10.1128/mcb.23.2.687-698.2003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateBase SequenceBinding SitesCodon, InitiatorEncephalomyocarditis virusEscherichia coliEukaryotic Initiation Factor-4AEukaryotic Initiation Factor-4GGene DeletionModels, BiologicalModels, MolecularMolecular Sequence DataPlasmidsProtein BindingProtein BiosynthesisProtein ConformationProtein Structure, SecondaryProtein Structure, TertiaryRibosomesRNASequence Homology, Nucleic AcidConceptsInternal ribosome entry siteEukaryotic initiation factor 2EIF4GCentral domainEukaryotic initiation factor 4GConformational changesInitiation factor 2K domainRibosome binding siteInitiation of translationInternal ribosomal entry siteEntry siteExtensive conformational rearrangementsThree-way helical junctionInitiation codon AUGRibosome entry siteEncephalomyocarditis virus internal ribosomal entry siteEncephalomyocarditis virus (EMCV) mRNAInitiation codonRibosomal complexesC-terminusIRES functionProductive bindingCodon AUGN-terminus
2000
The Functional Role of Basic Patch, a Structural Element ofEscherichia coli Transcript Cleavage Factors GreA and GreB*
Kulish D, Lee J, Lomakin I, Nowicka B, Das A, Darst S, Normet K, Borukhov S. The Functional Role of Basic Patch, a Structural Element ofEscherichia coli Transcript Cleavage Factors GreA and GreB*. Journal Of Biological Chemistry 2000, 275: 12789-12798. PMID: 10777576, DOI: 10.1074/jbc.275.17.12789.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceDose-Response Relationship, DrugEscherichia coliEscherichia coli ProteinsGenetic Complementation TestHydrogen-Ion ConcentrationIsopropyl ThiogalactosideModels, MolecularMolecular Sequence DataMutagenesisOligonucleotidesPlasmidsRNASequence Homology, Amino AcidTemperatureTranscription FactorsTranscription, GeneticTranscriptional Elongation FactorsConceptsTernary elongation complexTranscript cleavage reactionWild-type factorBasic patchLarge basic patchFunctional roleGre proteinsThermosensitive phenotypeTranscription elongationElongation complexNascent RNAGre factorsThree-dimensional structureRNA polymeraseTerminal domainVivo functionE. coli strainsGreAGreBEscherichia coliType factorsCleavage reactionColi strainsMutantsReadthrough