2025
Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin
Kim M, Kim J, Lee G, Olinares P, Airan Y, Chow J, Park J, Jeong Y, Park J, Chait B, Herzon S, Kim C, Kang J. Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin. Structure 2025 PMID: 40381618, DOI: 10.1016/j.str.2025.04.017.Peer-Reviewed Original ResearchNRPS-PKSCarrier proteinCryo-EM structurePKS enzymesPolyketide synthaseBiosynthesis mechanismBiosynthetic enzymesUpstream enzymesDimer interfaceColibactinBinding sitesDocking interactionsKetosynthasePromote colorectal cancerEnzymeStructural studiesGenomeBiosynthesisStructural detailsStructural analysisProteinGenotoxinsSynthaseHostCLBI
2024
Multiple mechanisms for licensing human replication origins
Yang R, Hunker O, Wise M, Bleichert F. Multiple mechanisms for licensing human replication origins. Nature 2024, 636: 488-498. PMID: 39604729, PMCID: PMC11910750, DOI: 10.1038/s41586-024-08237-8.Peer-Reviewed Original ResearchOrigin recognition complexReplication originsMCM loadingHexamer formationDNA replication initiationDNA replication machineryHuman replication originsOrc6 subunitMulticellular eukaryotesBiochemical reconstitutionReplication initiationRecognition complexReplicative helicaseMultiple mechanismsReplication machineryEukaryotic MCM2Helicase motorReplication stressOrigin licensingDimer interfaceOrc6Reconstituted systemYeastHexamerMCM2Development of Ligands and Degraders Targeting MAGE-A3
Li K, Krone M, Butrin A, Bond M, Linhares B, Crews C. Development of Ligands and Degraders Targeting MAGE-A3. Journal Of The American Chemical Society 2024, 146: 24884-24891. PMID: 39190582, DOI: 10.1021/jacs.4c05393.Peer-Reviewed Original ResearchDNA-encoded librariesSmall molecule ligandsDevelopment of ligandsE3 ligase complexCocrystal structureChemical matterLigandPROTAC moleculesSmall moleculesLigase complexTargeted Protein DegradationMAGE-A3Substrate recognition moduleType I MAGEsRING E3 ligasesMoleculesCancer-selective expressionDimer interfaceImprove immunotherapy outcomesIncreased antigen presentationHigh tumor gradeE3 ligaseComplexBiochemical functionsCancer cell surfaceCrystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase
Li H, Hardy C, Reidl C, Jing Q, Xue F, Cinelli M, Silverman R, Poulos T. Crystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase. Biochemistry 2024, 63: 788-796. PMID: 38417024, PMCID: PMC10956423, DOI: 10.1021/acs.biochem.3c00601.Peer-Reviewed Original ResearchConceptsHydrogen bondsHeme propionatesDimer interfaceInhibitor bindingCombination of crystallographyInhibitor binding siteDevelopment of isoform-selective inhibitorsIsoform-selective inhibitorsStructural basisComputational insightsStructural changesInhibitor moleculesChanges conformationBinding sitesConformational changesBondsSite inhibitorsPterin cofactorBindingHydrogenSynthaseDimerStructural differencesTyrosineInhibitors
2018
Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor
Nelson CA, Wilen CB, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e9201-e9210. PMID: 30194229, PMCID: PMC6166816, DOI: 10.1073/pnas.1805797115.Peer-Reviewed Original ResearchConceptsP domainCognate cellular receptorDomain dimer interfaceDimer interfaceBiophysical assaysStructural basisCD300lfResidue mutationsP2 subdomainAcid bindingCell surfaceHost ligandsCellular receptorsProtruding (P) domainStructural determinantsDE loopMonomeric affinityBinding sitesX-ray crystal structurePotential modulatorsReceptor binding sitesMNoVCrystal structureDivalent cationsReceptors
2017
Dimerization of Tie2 mediated by its membrane-proximal FNIII domains
Moore JO, Lemmon MA, Ferguson KM. Dimerization of Tie2 mediated by its membrane-proximal FNIII domains. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 4382-4387. PMID: 28396397, PMCID: PMC5410832, DOI: 10.1073/pnas.1617800114.Peer-Reviewed Original ResearchConceptsExtracellular regionFNIII domainsResolution X-ray crystal structureMembrane-proximal fibronectin type III domainsDomain-mediated interactionsDifferent cellular contextsLigand-binding regionHigher-order oligomersTie2 activationFibronectin type III domainReceptor tyrosine kinasesTyrosine kinase familyEGF-homology domainThird FNIII domainType III domainPrevious structural studiesStructural studiesHomology domainCellular contextKinase familyDimer interfaceDimerization modeReceptor dimerizationTyrosine kinasePrimary activator
2014
Structure of the Chicken CD3ϵδ/γ Heterodimer and Its Assembly with the αβT Cell Receptor*
Berry R, Headey S, Call M, McCluskey J, Tregaskes C, Kaufman J, Koh R, Scanlon M, Call M, Rossjohn J. Structure of the Chicken CD3ϵδ/γ Heterodimer and Its Assembly with the αβT Cell Receptor*. Journal Of Biological Chemistry 2014, 289: 8240-8251. PMID: 24488493, PMCID: PMC3961652, DOI: 10.1074/jbc.m113.544965.Peer-Reviewed Original ResearchConceptsTCR signaling complexSignaling ComplexIn vitro biochemical assaysPrimitive ancestral formAncestral formDimer interfaceSignaling apparatusSurface-exposedNMR structureNonconserved residuesSignaling moleculesHeterodimerSubunit arrangementBiochemical assaysBiochemical analysisCell receptorsChickenTransmembrane siteMammalsMolecular surfaceAssemblySubunitTCRReceptorsTCRA
2013
Mechanism for activation of mutated epidermal growth factor receptors in lung cancer
Brewer M, Yun CH, Lai D, Lemmon MA, Eck MJ, Pao W. Mechanism for activation of mutated epidermal growth factor receptors in lung cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e3595-e3604. PMID: 24019492, PMCID: PMC3780914, DOI: 10.1073/pnas.1220050110.Peer-Reviewed Original ResearchConceptsWT epidermal growth factor receptorEpidermal growth factor receptorTyrosine kinase domainGrowth factor receptorConformational changesAsymmetric dimer interfaceMutant epidermal growth factor receptorAllosteric conformational changeAsymmetric dimer formationFactor receptorIntermolecular regulationKinase domainEGFR tyrosine kinase domainDimer interfaceMutantsM mutantActive conformation
2011
Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases
Shih AJ, Telesco SE, Choi SH, Lemmon MA, Radhakrishnan R. Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases. Biochemical Journal 2011, 436: 241-251. PMID: 21426301, PMCID: PMC3138537, DOI: 10.1042/bj20101791.Peer-Reviewed Original ResearchConceptsErbB familyDifferent molecular contextsIntracellular kinase domainImportant regulatory elementsSrc kinase HckReceptor tyrosine kinasesHomologous receptor tyrosine kinasesSequence similarityKinase domainRegulatory elementsDimer interfaceSubdomain motionsInactive conformationKey residuesEGFR activationMolecular contextTyrosine kinasePresent molecular dynamics studyBond networkActive conformationConformational statesKinaseErbB kinasesMolecular dynamics analysisSalt bridge
2009
Functional correlation of bacterial LuxS with their quaternary associations: interface analysis of the structure networks
Bhattacharyya M, Vishveshwara S. Functional correlation of bacterial LuxS with their quaternary associations: interface analysis of the structure networks. BMC Molecular And Cell Biology 2009, 9: 8. PMID: 19243584, PMCID: PMC2656534, DOI: 10.1186/1472-6807-9-8.Peer-Reviewed Original ResearchConceptsProtein structure networksSequence alignment studiesQuorum sensing moleculesDesign of inhibitorsHigh structural similarityCertain structural detailsGene homologuesStructure comparison methodsFlagellar motilityLux genesHomodimeric proteinDimer interfaceDimeric interfaceAI-2Protein interfacesVariety of functionsQuaternary associationMetabolic regulationSensing moleculesFunctional roleStructure networkProkaryotesX-ray crystallographyProteinToxin production
2008
Human Quiescin-Sulfhydryl Oxidase, QSOX1: Probing Internal Redox Steps by Mutagenesis
Heckler E, Alon A, Fass D, Thorpe C. Human Quiescin-Sulfhydryl Oxidase, QSOX1: Probing Internal Redox Steps by Mutagenesis. Biochemistry 2008, 47: 4955-4963. PMID: 18393449, PMCID: PMC3542536, DOI: 10.1021/bi702522q.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsCatalysisCattleCysteineDisulfidesEgg ProteinsGene Expression Regulation, BacterialHumansMilk ProteinsMolecular Sequence DataMutagenesisOxidation-ReductionOxidoreductases Acting on Sulfur Group DonorsProtein FoldingProtein Structure, TertiaryRecombinant ProteinsSequence Analysis, ProteinSequence Homology, Amino AcidThioredoxinsConceptsQuiescin sulfhydryl oxidaseThioredoxin domainInserts disulfide bondsRecombinant expression systemProximal disulfideAvian enzymeEnzymological characterizationHeterologous expressionEnzyme familyErv/ALR domainDimer interfaceExpression systemPolypeptide chainOxygen to hydrogen peroxideReducing equivalentsCysteine residuesMechanistic dissectionFlavin ringCysteine mutantsRNaseActivity assayAvian eggsReduction of oxygen to hydrogen peroxideDisulfide bondsRedox steps
2005
Control of the CFTR channel's gates
Vergani P, Basso C, Mense M, Nairn A, Gadsby D. Control of the CFTR channel's gates. Biochemical Society Transactions 2005, 33: 1003-1007. DOI: 10.1042/bst0331003.Peer-Reviewed Original ResearchChannel gateIon channelsProtein family membersNBD dimer interfaceAnion-selective poreEvolutionary conservationABC proteinsCFTR moleculesForm homodimersTransmembrane domainATP bindingHeterodimer interfaceDimer interfaceMolecular mechanismsTight dimerizationNBDATPSingle-channel recordingsResiduesFamily membersNBD1NBD2Cystic fibrosis patientsMutagenesisHomodimerControl of the CFTR channel's gates.
Vergani P, Basso C, Mense M, Nairn A, Gadsby D. Control of the CFTR channel's gates. Biochemical Society Transactions 2005, 33: 1003-7. PMID: 16246032, PMCID: PMC2728124, DOI: 10.1042/bst20051003.Peer-Reviewed Original ResearchConceptsChannel gateIon channelsProtein family membersNBD dimer interfaceAnion-selective poreEvolutionary conservationABC proteinsCFTR moleculesForm homodimersTransmembrane domainATP bindingHeterodimer interfaceDimer interfaceMolecular mechanismsTight dimerizationNBDATPSingle-channel recordingsResiduesFamily membersNBD1NBD2Cystic fibrosis patientsMutagenesisHomodimer
2004
The X-Ray Structure of an Antiparallel Dimer of the Human Amyloid Precursor Protein E2 Domain
Wang Y, Ha Y. The X-Ray Structure of an Antiparallel Dimer of the Human Amyloid Precursor Protein E2 Domain. Molecular Cell 2004, 15: 343-353. PMID: 15304215, DOI: 10.1016/j.molcel.2004.06.037.Peer-Reviewed Original ResearchConceptsMembrane protein precursorsX-ray structureSpectrin familyHeparan sulfate proteoglycanDimer interfaceBiological functionsStructure of E2Protein structureProtein precursorPutative ligandE2 domainContinuous helixExtracellular matrixUnexpected resemblanceAntiparallel dimerSulfate proteoglycanAntiparallel orientationPrecursor presentDomainBindsHelixDimerizationSecond monomerAn Intersubunit Disulfide Bond Prevents in Vitro Aggregation of a Superoxide Dismutase-1 Mutant Linked to Familial Amytrophic Lateral Sclerosis †
Ray SS, Nowak RJ, Strokovich K, Brown RH, Walz T, Lansbury PT. An Intersubunit Disulfide Bond Prevents in Vitro Aggregation of a Superoxide Dismutase-1 Mutant Linked to Familial Amytrophic Lateral Sclerosis †. Biochemistry 2004, 43: 4899-4905. PMID: 15109247, DOI: 10.1021/bi030246r.Peer-Reviewed Original ResearchConceptsSuperoxide dismutase 1Familial amyotrophic lateral sclerosisDisulfide bondsDisease-associated proteinsIntersubunit disulfide bondsWild-type SOD1Symmetry-related residuesWild-type superoxide dismutase 1Dimer interfaceMutant formsAmyloid poresMutant superoxide dismutase 1Pathogenic speciesAmytrophic lateral sclerosisAbolished aggregationConcentration-dependent lossSOD1 inclusionsVitro aggregationPoint mutationsDimer dissociationEnzymatic activityWT dimerLateral sclerosisDismutase 1Animal modeling studies
2001
Specificity in transmembrane helix–helix interactions can define a hierarchy of stability for sequence variants
Fleming K, Engelman D. Specificity in transmembrane helix–helix interactions can define a hierarchy of stability for sequence variants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 14340-14344. PMID: 11724930, PMCID: PMC64683, DOI: 10.1073/pnas.251367498.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesDimerizationDrug StabilityElectrophoresis, Polyacrylamide GelGenetic VariationGlycophorinsHumansIn Vitro TechniquesMagnetic Resonance SpectroscopyMembrane ProteinsMutagenesis, Site-DirectedPoint MutationProtein FoldingProtein Structure, SecondaryRecombinant Fusion ProteinsThermodynamicsUltracentrifugationConceptsHelix-helix interactionsMembrane proteinsTransmembrane helix-helix interactionsSequence variantsHelical membrane proteinsTransmembrane helix dimerizationProtein-protein interactionsDifferent hydrophobic environmentsAlanine-scanning mutagenesisSedimentation equilibrium analytical ultracentrifugationEquilibrium analytical ultracentrifugationTransmembrane helicesHelix dimerizationGxxxG motifDimer interfaceNMR structureDimer stabilityAnalytical ultracentrifugationHydrophobic environmentProteinMutationsSequence dependenceEnergetic principlesHierarchy of stabilityMutagenesisIdentification of the transmembrane dimer interface of the bovine papillomavirus E5 protein
Mattoon D, Gupta K, Doyon J, Loll P, DiMaio D. Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein. Oncogene 2001, 20: 3824-3834. PMID: 11439346, DOI: 10.1038/sj.onc.1204523.Peer-Reviewed Original ResearchConceptsBovine papillomavirus E5 proteinE5 proteinDimer interfacePlatelet-derived growth factor β receptorEssential glutamine residueHeterologous dimerization domainGrowth factor β receptorNon-productive interactionsReceptor tyrosine phosphorylationFocus formation assayPDGF β-receptorDimerization domainHomodimeric proteinTyrosine phosphorylationGenetic methodsGlutamine residuesActive chimerasΒ receptorActive orientationFormation assaysProtein helicesProteinPosition 17ReceptorsPhosphorylation
1998
Structure-based prediction of the stability of transmembrane helix–helix interactions: The sequence dependence of glycophorin A dimerization
MacKenzie K, Engelman D. Structure-based prediction of the stability of transmembrane helix–helix interactions: The sequence dependence of glycophorin A dimerization. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 3583-3590. PMID: 9520409, PMCID: PMC19879, DOI: 10.1073/pnas.95.7.3583.Peer-Reviewed Original ResearchConceptsHelix-helix interactionsTransmembrane helix-helix associationTransmembrane helix-helix interactionsHelix-helix associationSingle-point mutantsStructure-based predictionTransmembrane domainMembrane proteinsDimer interfaceDimerization propensitySide-chain hydrophobicityDimer stabilityPoint mutationsSteric clashesMultiple mutationsMutationsSequence dependenceCompensatory effectFavorable van der Waals interactionsMutantsFoldingProteinInteractionDimerizationGlycophorin
1996
Leucine side-chain rotamers in a glycophorin A transmembrane peptide as revealed by three-bond carbon—carbon couplings and 13C chemical shifts
MacKenzie K, Prestegard J, Engelman D. Leucine side-chain rotamers in a glycophorin A transmembrane peptide as revealed by three-bond carbon—carbon couplings and 13C chemical shifts. Journal Of Biomolecular NMR 1996, 7: 256-260. PMID: 8785502, DOI: 10.1007/bf00202043.Peer-Reviewed Original ResearchConceptsChemical shiftsPeptide dimersΑ-carbonSide chainsSide-chain rotamer populationsCarbon-carbon couplingLeucine side chainsThree-bond J couplingsNMR pulse sequencesΔ-methyl groupsRotamer populationsMethyl carbonFast exchangeSide-chain rotamersJ-couplingsTransmembrane peptidesDimer interfaceRotameric statesProtein systemsRotamersShift distributionGlycophorin A.DimersChainMethylEscherichia coli Tryptophanyl-tRNA Synthetase Mutants Selected for Tryptophan Auxotrophy Implicate the Dimer Interface in Optimizing Amino Acid Binding †
Sever S, Rogers K, Rogers M, Carter C, Söll D. Escherichia coli Tryptophanyl-tRNA Synthetase Mutants Selected for Tryptophan Auxotrophy Implicate the Dimer Interface in Optimizing Amino Acid Binding †. Biochemistry 1996, 35: 32-40. PMID: 8555191, DOI: 10.1021/bi952103d.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacillus subtilisBase SequenceBinding SitesCloning, MolecularDNA PrimersEscherichia coliGenes, BacterialGeobacillus stearothermophilusHaemophilus influenzaeKineticsMacromolecular SubstancesModels, MolecularMolecular Sequence DataPolymerase Chain ReactionProtein FoldingProtein Structure, SecondaryRecombinant ProteinsRestriction MappingSequence Homology, Amino AcidTryptophanTryptophan-tRNA LigaseConceptsTryptophanyl-tRNA synthetaseDimer interfaceClass I aminoacyl-tRNA synthetasesAminoacyl-tRNA synthetasesAmino acid bindingAmino acid activationActive siteSteady-state kinetic analysisSynthetase mutantsRossmann foldApparent KmKMSKS loopTrp lociProtein structureTrpR proteinTryptophan auxotrophDimeric enzymeAuxotrophic strainsBacillus stearothermophilusAcid bindingEscherichia coliOptimal catalysisAminoacyl adenylatesMutantsMutations
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