Featured Publications
Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism
Lomakin I, Devarkar S, Patel S, Grada A, Bunick C. Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Nucleic Acids Research 2023, 51: 2915-2930. PMID: 36864821, PMCID: PMC10085706, DOI: 10.1093/nar/gkad103.Peer-Reviewed Original ResearchMeSH KeywordsAcne VulgarisAnti-Bacterial AgentsHumansPropionibacterium acnesProtein BiosynthesisRibosomesTetracyclinesNonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA
Yuan S, Peng L, Park JJ, Hu Y, Devarkar SC, Dong MB, Shen Q, Wu S, Chen S, Lomakin IB, Xiong Y. Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. Molecular Cell 2020, 80: 1055-1066.e6. PMID: 33188728, PMCID: PMC7833686, DOI: 10.1016/j.molcel.2020.10.034.Peer-Reviewed Original ResearchConceptsInternal ribosome entry site RNANonstructural protein 1Host protein synthesis machineryMRNA entry channelProtein synthesis machineryCryo-EM structureProtein 1Major pathogenicity factorsDifferential expression analysisMRNA-seq dataCellular transcriptomePreinitiation complexSynthesis machineryHuman lung originTranslation inhibitionPathogenicity factorsExpression analysisSite RNAHost viabilityNSP1Protein synthesisEntry channelViral proteinsUnknown mechanismViral RNAPhysical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of Translation
Lomakin I, Hellen C, Pestova T. Physical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of Translation. Molecular And Cellular Biology 2000, 20: 6019-6029. PMID: 10913184, PMCID: PMC86078, DOI: 10.1128/mcb.20.16.6019-6029.2000.Peer-Reviewed Original ResearchConceptsInternal ribosomal entry siteEMCV internal ribosomal entry siteEIF4GAdditional amino-terminal sequenceEukaryotic initiation factor 4GRNA recognition motifEukaryotic initiation factor 4GIInternal ribosomal entryEntry siteComplex formationBeta-globin mRNAAmino-terminal sequenceEncephalomyocarditis virus internal ribosomal entry siteRibosomal entryRecognition motifLike domainMutational analysisPhysical associationInternal initiationHigh-affinity bindingBinding fragmentSpecific interactionsRNASimilar affinitySpecific high-affinity bindingA 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 componentDomainMutagenesisDendritic BC1 RNA: Functional Role in Regulation of Translation Initiation
Wang H, Iacoangeli A, Popp S, Muslimov IA, Imataka H, Sonenberg N, Lomakin IB, Tiedge H. Dendritic BC1 RNA: Functional Role in Regulation of Translation Initiation. Journal Of Neuroscience 2002, 22: 10232-10241. PMID: 12451124, PMCID: PMC1828542, DOI: 10.1523/jneurosci.22-23-10232.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain ChemistryCell-Free SystemCells, CulturedDendritesElectrophoretic Mobility Shift AssayEukaryotic Initiation Factor-4AEukaryotic Initiation FactorsGene Expression RegulationMacromolecular SubstancesNeuronal PlasticityNeuronsPeptide Chain Initiation, TranslationalPoly(A)-Binding ProteinsProtein BiosynthesisRatsRats, Sprague-DawleyRepressor ProteinsRibosomesRNA, MessengerRNA, Small CytoplasmicConceptsLocal protein synthesisBC1 RNATranslation initiationInternal ribosome entry mechanismCap-dependent translation initiationProtein synthesisFunctional roleMessenger RNASmall ribosomal subunitTranslational control mechanismsLevel of initiationDendritic BC1 RNAPlasticity of synapsesRepression pathwaySpecific repressorPreinitiation complexTranslational controlInitiation factorsRibosomal subunitBiochemical experimentsLocal translationInternal initiationRNAEntry mechanismDensity gradient centrifugationThe initiation of mammalian protein synthesis and mRNA scanning mechanism
Lomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature 2013, 500: 307-311. PMID: 23873042, PMCID: PMC3748252, DOI: 10.1038/nature12355.Peer-Reviewed Original ResearchConceptsSmall ribosomal subunitTranslation initiationRibosomal subunitMammalian translation initiationProtein synthesisInitiator transfer RNAMammalian protein synthesisMultiple initiation factorsMRNA scanningTransfer RNAInitiation factorsInitiation codonConformational changesMessenger RNAFunctional implicationsEukaryotesDistinct stepsP siteSubunitsRNAFunctional stateEIF1ARibosomesEIF1Codon
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
2003
Eukaryotic 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