Featured Publications
The 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 subunitsCrystal 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
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
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
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