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 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 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 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 stateEIF1ARibosomesEIF1CodonCrystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation
Lomakin IB, Dmitriev SE, Steitz TA. Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 528-533. PMID: 30584092, PMCID: PMC6329987, DOI: 10.1073/pnas.1809688116.Peer-Reviewed Original ResearchConceptsTranslation initiationHeterodimer formationUnconventional translation initiationNoncanonical translation initiationZinc-binding siteMechanism of regulationUpstream reading framesIon-binding sitesRibosome recyclingReading frameTerminal domainTranslation reinitiationCysteine residuesAtomic detailHeterodimersMCT-1Crystal structureSpecific setReinitiationRibosomesProteinCysteineMRNAResiduesSites
2020
Crystal structure of the C-terminal domain of DENR
Lomakin IB, De S, Wang J, Borkar AN, Steitz TA. Crystal structure of the C-terminal domain of DENR. Computational And Structural Biotechnology Journal 2020, 18: 696-704. PMID: 32257053, PMCID: PMC7114459, DOI: 10.1016/j.csbj.2020.03.009.Peer-Reviewed Original ResearchNon-canonical translation initiationTerminal domainTranslation initiationRibosomal recyclingSequence homology modelingSmall ribosomal subunitInitiation factor eIF1N-terminal domainInitiation codon selectionMCT-1Low-resolution crystal structureIon-binding sitesStable heterodimerRibosomal subunitCodon selectionÅ resolutionSimilar foldHomology modelingHelix h44EIF1DENRRRNAP siteCrystal structureHeterodimers
2017
Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation Initiation
Vaidya AT, Lomakin IB, Joseph NN, Dmitriev SE, Steitz TA. Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation Initiation. Journal Of Molecular Biology 2017, 429: 2765-2771. PMID: 28736176, PMCID: PMC5572308, DOI: 10.1016/j.jmb.2017.07.015.Peer-Reviewed Original ResearchConceptsTranslation initiationProtein synthesisEukaryotic translation initiationSmall ribosomal subunitTranslation initiation factorInitiation factor 2C-terminal domainInitiation codon selectionInter-domain interactionsCellular protein synthesisRibosome recyclingCertain mRNAsInitiation factorsRibosomal subunitTerminal domainCodon selectionInitiator tRNAMolecular mechanismsΑ-subunitInitiation pathwayTerminal partAtomic detailStress conditionsEIF2DSecond domainCrystal Structure of the Human Ribosome in Complex with DENR-MCT-1
Lomakin IB, Stolboushkina EA, Vaidya AT, Zhao C, Garber MB, Dmitriev SE, Steitz TA. Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell Reports 2017, 20: 521-528. PMID: 28723557, PMCID: PMC5551485, DOI: 10.1016/j.celrep.2017.06.025.Peer-Reviewed Original ResearchConceptsSmall ribosomal subunitTranslation initiationRibosomal subunitUnconventional translation initiationInitiation factor 1Cancer-related mRNAsTranslational controlHuman ribosomeTerminal domainReinitiation stepsRibosomesDimer interactsFunctional implicationsFactor 1SubunitsCrystal structureStriking similaritySpecific setComplexesHeterodimersProteinOncoproteinInitiationInteractsMRNA