Featured Publications
Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assembly
Eldirany SA, Ho M, Hinbest AJ, Lomakin IB, Bunick CG. Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assembly. The EMBO Journal 2019, 38: embj2018100741. PMID: 31036554, PMCID: PMC6545558, DOI: 10.15252/embj.2018100741.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionCircular DichroismCrystallography, X-RayCytoskeletonDynamic Light ScatteringHumansHydrophobic and Hydrophilic InteractionsIntermediate Filament ProteinsKeratin-1Keratin-10Models, MolecularMutation, MissenseProtein FoldingProtein Interaction Domains and MotifsProtein MultimerizationProtein Structure, QuaternaryProtein Structure, SecondarySkin DiseasesConceptsFilament assemblyN-terminal hydrophobic pocketIntermediate filament assemblyTetramer assemblyÅ structureÅ resolutionCircular dichroism measurementsTetramer formationAssembly mechanismHydrophobic faceHydrophobic pocketSecondary structureOctamer structureEpidermolytic palmoplantar keratodermaKeratin filamentsIntermediate filamentsMutationsPathogenic mutationsTetramer structureDichroism measurementsAtomic resolutionAssemblyBiochemical determinantsKeratin 1/10TetramerPosition of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing
Unbehaun A, Marintchev A, Lomakin IB, Didenko T, Wagner G, Hellen C, Pestova TV. Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. The EMBO Journal 2007, 26: 3109-3123. PMID: 17568775, PMCID: PMC1914099, DOI: 10.1038/sj.emboj.7601751.Peer-Reviewed Original ResearchThe Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together
Lomakin IB, Xiong Y, Steitz TA. The Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together. Cell 2007, 129: 319-332. PMID: 17448991, DOI: 10.1016/j.cell.2007.03.013.Peer-Reviewed Original ResearchConceptsCatalytic siteCrystal structureAcyl carrier proteinPantetheine armActive siteCatalytic centerMacromolecular assembliesYeast fatty acid synthaseReaction chamberKetoacyl synthase domainWhole metabolic pathwaysTwo-dimensional diffusionAssemblyCarrier proteinSynthesisStructureComplexesCellular machinesMultiple stepsAcidSitesShellSubstrateRecent insight into intermediate filament structure
Eldirany SA, Lomakin IB, Ho M, Bunick CG. Recent insight into intermediate filament structure. Current Opinion In Cell Biology 2020, 68: 132-143. PMID: 33190098, PMCID: PMC7925366, DOI: 10.1016/j.ceb.2020.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCytoskeletonHumansIntermediate Filament ProteinsIntermediate FilamentsLaminsModels, MolecularMutationConceptsIntermediate filamentsAssembly mechanismVariable N-terminalMultiple cellular processesCentral rod domainIntermediate filament structureCoil 1BCellular processesStudy of keratinsTail domainFilament assemblyRod domainC-terminalN-terminalElectrostatic surfacePathologic mutationsKey playersFilament structureRecent insightsComplex formationProteinHuman tissuesGlial fibrillary acidic proteinAcidic proteinDomainPosition 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 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 stateEIF1ARibosomesEIF1CodonThe mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin
Roy RN, Lomakin IB, Gagnon MG, Steitz TA. The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nature Structural & Molecular Biology 2015, 22: 466-469. PMID: 25984972, PMCID: PMC4456192, DOI: 10.1038/nsmb.3031.Peer-Reviewed Original Research
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 domain
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
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