Featured Publications
Nonstructural 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 RNAMolecular 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 ResearchDendritic 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 centrifugationPosition of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing
Lomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes & Development 2003, 17: 2786-2797. PMID: 14600024, PMCID: PMC280627, DOI: 10.1101/gad.1141803.Peer-Reviewed Original ResearchAnimalsBinding SitesCodon, InitiatorEukaryotic Initiation Factor-1Eukaryotic Initiation Factor-3HumansHydroxyl RadicalModels, MolecularNucleic Acid ConformationPeptide Chain Initiation, TranslationalProtein BindingProtein FootprintingProtein Structure, TertiaryProtein SubunitsRecombinant Fusion ProteinsRibosomesRNA, MessengerRNA, RibosomalThe 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 3GTPComplexesEukaryotesEIF5EIF5BEIF2EIF4BEIF1ARibosomesIF2The 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
2023
Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses
Devarkar S, Vetick M, Balaji S, Lomakin I, Yang L, Jin D, Gilbert W, Chen S, Xiong Y. Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses. Cell Reports 2023, 42: 113156. PMID: 37733586, DOI: 10.1016/j.celrep.2023.113156.Peer-Reviewed Original ResearchConceptsMERS-CoV nsp1Translation inhibitionRibosomal subunitΒ-CoVsModest sequence conservationMRNA entry channelEssential pathogenicity factorHost gene expressionHuman 40S ribosomal subunitSARS-CoV-2 nsp1Cryogenic electron microscopySequence conservationNon-structural protein 1Terminal domainPathogenicity factorsStructural basisGene expressionDevelopment of antiviralsNSP1Entry channelProtein 1Potential therapeutic targetSubunitsExtensive interactionsTherapeutic target
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