2020
Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases
Sheetz JB, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttilä R, Preuss F, Suresh K, Stayrook SE, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon MA. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. Molecular Cell 2020, 79: 390-405.e7. PMID: 32619402, PMCID: PMC7543951, DOI: 10.1016/j.molcel.2020.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBaculoviridaeBinding SitesCell Adhesion MoleculesCell LineCloning, MolecularCrystallography, X-RayGene ExpressionHumansMiceModels, MolecularPrecursor Cells, B-LymphoidProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsProtein Kinase InhibitorsReceptor Protein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsReceptors, Eph FamilyRecombinant ProteinsSf9 CellsSmall Molecule LibrariesSpodopteraStructural Homology, ProteinSubstrate SpecificityConceptsInsulin receptor kinasePseudokinase domainReceptor tyrosine kinasesTyrosine kinaseNon-catalytic functionsATP-binding pocketType II inhibitorsDomain plasticityActivation loopReceptor kinaseInactive conformationStructural insightsPseudokinasesATP siteStructural comparisonAromatic residuesKinaseAlternative interactionsApparent lackImportant roleDomainWntMotifROR1Residues
2015
Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site
Moravcevic K, Alvarado D, Schmitz KR, Kenniston JA, Mendrola JM, Ferguson KM, Lemmon MA. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. Structure 2015, 23: 352-363. PMID: 25620000, PMCID: PMC4319572, DOI: 10.1016/j.str.2014.12.009.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCrystallography, X-RayGreen Fluorescent ProteinsGTPase-Activating ProteinsHeLa CellsHumansInositol PhosphatesModels, MolecularMolecular Sequence DataProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSpecies SpecificityConceptsF-BAR domainLipid-binding specificityMembrane-binding propertiesNumerous functional studiesPhosphate binding siteUnappreciated determinantF-BARDomain bindsCell signalingCurved membranesMembrane interactionsFunctional studiesRgd1pBinding sitesX-ray crystal structureInositol phosphatesDomain structureDomainHof1pPhospholipidsRhoGAPCytokinesisEndocytosisPhosphoinositideSignaling
2014
Putting together structures of epidermal growth factor receptors
Bessman NJ, Freed DM, Lemmon MA. Putting together structures of epidermal growth factor receptors. Current Opinion In Structural Biology 2014, 29: 95-101. PMID: 25460273, PMCID: PMC4268130, DOI: 10.1016/j.sbi.2014.10.002.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth factor receptorIntact epidermal growth factor receptorChemical biology methodsNumerous crystal structuresFactor receptorTyrosine kinase domainVariety of inhibitorsKinase domainExtracellular regionMembrane environmentIntracellular regionBiology methodsIntact receptorReceptorsCancer therapyNext challengeCrystal structureMembraneActivationRegionInhibitorsDomain
2010
Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids
Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids. Cell 2010, 143: 966-977. PMID: 21145462, PMCID: PMC3031122, DOI: 10.1016/j.cell.2010.11.028.Peer-Reviewed Original ResearchConceptsKA1 domainBud neck localizationMembrane association domainAcidic phospholipidsImportance of phosphatidylserineAssociation domainMembrane associationMembrane localizationProtein kinaseC2 domainC-terminusMembrane targetsKinaseIntact proteinAnionic phospholipidsX-ray crystallographyNeck localizationPhosphatidylserinePhospholipidsCrucial roleDomainMembrane surfaceLocalizationTerminusRegulatorCell Signaling by Receptor Tyrosine Kinases
Lemmon MA, Schlessinger J. Cell Signaling by Receptor Tyrosine Kinases. Cell 2010, 141: 1117-1134. PMID: 20602996, PMCID: PMC2914105, DOI: 10.1016/j.cell.2010.06.011.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTyrosine kinaseIntracellular tyrosine kinase domainRecent structural studiesGrowth factor ligandsTyrosine kinase domainUnexpected diversityKinase domainCell signalingLigand bindingCellular responsesFactor ligandRTK mutationsKinaseStructural studiesActivationSignalingDiversityMutationsDimerizationMechanismBindingDomain
2009
Characterization of Novel PtdIns(4,5)P2 Effector Domains
Moravcevic K, Lemmon M. Characterization of Novel PtdIns(4,5)P2 Effector Domains. The FASEB Journal 2009, 23: 873.6-873.6. DOI: 10.1096/fasebj.23.1_supplement.873.6.Peer-Reviewed Original ResearchEffector domainPrevious genome-wide studiesPhosphoinositide-binding proteinsKey cellular processesGenome-wide studiesDifferent protein domainsEffector proteinsCellular functionsCellular processesProtein domainsBiochemical approachesS. cerevisiaeBiochemical basisCellular activitiesCandidate novelDirect interactionProteinNew insightsDomainCerevisiaeMajor rolePhosphoinositideBiologyEffectorsDiversity
2008
Structural basis for EGFR ligand sequestration by Argos
Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA. Structural basis for EGFR ligand sequestration by Argos. Nature 2008, 453: 1271-1275. PMID: 18500331, PMCID: PMC2526102, DOI: 10.1038/nature06978.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell LineCrystallography, X-RayDrosophila melanogasterDrosophila ProteinsEpidermal Growth FactorErbB ReceptorsEye ProteinsHumansLigandsMembrane ProteinsModels, MolecularNerve Tissue ProteinsProtein Structure, TertiaryReceptors, Transforming Growth Factor betaSpodopteraConceptsEpidermal growth factor receptorLigand sequestrationEGFR ligand SpitzLigand SpitzMammalian counterpartsGrowth factor receptorStructural basisUrokinase plasminogen activatorStructural homologuesEGFR ligandsFactor receptorAnticancer therapeuticsStructural resemblanceHomologuesPlasminogen activatorReceptorsSequestrationProteinActivatorLigandsSpitzTGFTherapeuticsDomain
2003
Molecular Determinants of tGolgin-1 Function
Yoshino A, Marks M, Lemmon M. Molecular Determinants of tGolgin-1 Function. 2003 DOI: 10.21236/ada418143.Peer-Reviewed Original ResearchTrans-Golgi networkGRIP domainMammalian cellsC-terminal GRIP domainDynein/dynactin complexGRIP domain proteinsPeripheral membrane proteinsGTPase cascadeDomain proteinsDynactin complexGolgi networkMembrane proteinsCell motilityTurn bindsGolgi complexProtein resultsMolecular determinantsProteinTumor developmentOrthologuesCellsDomainRNAiEndosomesYeastPhosphoinositide Recognition Domains
Lemmon MA. Phosphoinositide Recognition Domains. Traffic 2003, 4: 201-213. PMID: 12694559, DOI: 10.1034/j.1600-0854.2004.00071.x.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainPhox homologyHomology domainEpsin ENTH domainENTH domainMembrane recruitmentFYVE domainBind phosphoinositidesTargeting domainsCellular phosphoinositidesCellular signalingCytoskeletal remodelingLipid bindingIntracellular traffickingStructural basisDistinct functionsExquisite specificityRecognition domainPhosphoinositideSpecificity characteristicsBilayer curvatureSignificant insightsHigh affinityDomainHomologyGenome-wide analysis of signaling domain function
Yu JW, Lemmon MA. Genome-wide analysis of signaling domain function. Current Opinion In Chemical Biology 2003, 7: 103-109. PMID: 12547434, DOI: 10.1016/s1367-5931(02)00008-x.Peer-Reviewed Original ResearchChapter 150 Pleckstrin Homology (PH) Domains
Lemmon M. Chapter 150 Pleckstrin Homology (PH) Domains. 2003, 161-169. DOI: 10.1016/b978-012124546-7/50511-8.Peer-Reviewed Original ResearchPleckstrin homology domainPH domainHomology domainSequence similarityPH domain-containing proteinsDomain-containing proteinsHuman genome sequenceMembrane traffickingConserved motifsMembrane associationCommon foldCellular signalingGenome sequenceCytoskeletal organizationDomain familySequence identityFunctional relatednessProtein ligandsHigh affinityProteinPhospholipid modificationStructural similarityPhosphoinositideSequenceDomain
2002
Molecular Determinants of tGolgin-1 Function
Yoshino A, Marks M, Lemmon M. Molecular Determinants of tGolgin-1 Function. 2002 DOI: 10.21236/ada408101.Peer-Reviewed Original ResearchTrans-Golgi networkGRIP domainC-terminal GRIP domainGRIP domain proteinsPeripheral membrane proteinsN-terminal domainDomain proteinsGolgi networkTGN structureMammalian cellsGolgin-97Membrane proteinsCell motilityMolecular basisGolgi complexMolecular determinantsBroader roleCoil regionProteinTumor metastasisProtein contentCellsDomainRNAiMicrotubules
2001
High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization †
Sankaran V, Klein D, Sachdeva M, Lemmon M. High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization †. Biochemistry 2001, 40: 8581-8587. PMID: 11456498, DOI: 10.1021/bi010425d.Peer-Reviewed Original ResearchMeSH KeywordsBinding, CompetitiveBlood ProteinsCarrier ProteinsCation Transport ProteinsGlutathione TransferaseGuanine Nucleotide Exchange FactorsHeLa CellsHumansLiposomesMonosaccharide Transport ProteinsPhosphatidylinositol PhosphatesPhospholipidsPhosphoproteinsProtein BindingProtein Structure, TertiaryProteinsRecombinant Fusion ProteinsSymportersZinc FingersConceptsFYVE domainPH domainDomain oligomerizationSpecific PH domainsVacuolar protein sortingPleckstrin homology domainLipid headgroupsProtein sortingMembrane trafficHomology domainSpecific phosphoinositideLike domainEndosomal maturationHigh-affinity bindingPreferred lipidPhospholipase CPhosphoinositideIntact lipidsIntact phospholipidsOligomerizationDomainMembrane
2000
Structural Basis for Discrimination of 3-Phosphoinositides by Pleckstrin Homology Domains
Ferguson K, Kavran J, Sankaran V, Fournier E, Isakoff S, Skolnik E, Lemmon M. Structural Basis for Discrimination of 3-Phosphoinositides by Pleckstrin Homology Domains. Molecular Cell 2000, 6: 373-384. PMID: 10983984, DOI: 10.1016/s1097-2765(00)00037-x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceBinding SitesBlood ProteinsCrystallography, X-RayFatty AcidsHydrogen BondingInositol PhosphatesLipoproteinsModels, MolecularMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphatidylinositolsProtein Structure, SecondarySequence AlignmentSequence Homology, Amino AcidSignal TransductionSrc Homology DomainsSubstrate SpecificityConceptsPleckstrin homology domainPH domainHomology domainDifferent PH domainsPhosphoinositide specificityMembrane recruitmentProtein modulesCellular signalingStructural basisHost proteinsSecond messengerMajor PIAmino acidsX-ray crystal structureProteinDomainPhosphoinositideHead groupsSignalingMessengerBindsCrystal structureRecruitment
1999
Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1 mutant with a defective pleckstrin homology domain
Lee A, Frank D, Marks M, Lemmon M. Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1 mutant with a defective pleckstrin homology domain. Current Biology 1999, 9: 261-265. PMID: 10074457, DOI: 10.1016/s0960-9822(99)80115-8.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainPH domainReceptor-mediated endocytosisDynamin 1Homology domainEndocytic vesiclesPH domain bindsDynamin PH domainDominant negative inhibitorHigher-order oligomersDominant-negative inhibitionDynamin functionDomain bindsDynamin oligomersGTP bindingGTP hydrolysisGTPase activityPlasma membraneDynaminEndocytosisVesiclesPhosphoinositideBindsDomainMembrane
1997
Regulatory recruitment of signalling molecules to the cell membrane by pleckstrinhomology domains
M.A. L, M. F, J. S, K. F. Regulatory recruitment of signalling molecules to the cell membrane by pleckstrinhomology domains. Trends In Cell Biology 1997, 7: 237-242. PMID: 17708952, DOI: 10.1016/s0962-8924(97)01065-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCell membraneSmall protein modulesPleckstrin homology domainPH domainProtein modulesBiological functionsDiverse processesCertain proteinsSpecific membraneProtein synthesisCell adhesionDNA synthesisProteinMembraneRecent studiesRecruitmentDomainPhosphoinositideEfficient mechanismRegulationPathwayCellsFunctionAdhesionSpecific role for the PH domain of dynamin‐1 in the regulation of rapid endocytosis in adrenal chromaffin cells
Artalejo C, Lemmon M, Schlessinger J, Palfrey H. Specific role for the PH domain of dynamin‐1 in the regulation of rapid endocytosis in adrenal chromaffin cells. The EMBO Journal 1997, 16: 1565-1574. PMID: 9130701, PMCID: PMC1169760, DOI: 10.1093/emboj/16.7.1565.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal MedullaAmino Acid SequenceAnimalsBlood ProteinsCattleChromaffin CellsDynamin IDynaminsEndocytosisGenetic VariationGTP PhosphohydrolasesHumansModels, StructuralMolecular Sequence DataMutagenesis, Site-DirectedPatch-Clamp TechniquesPhosphoproteinsPolymerase Chain ReactionProtein Structure, SecondaryRecombinant ProteinsSequence Homology, Amino AcidConceptsPH domainDynamin 1Rapid endocytosisPleckstrin homology domainAmino acidsDynamin PH domainIsolated PH domainTypes of endocytosisChromaffin cellsHomology domainDynamin 2Mutational studiesEquivalent residuesEndocytotic processDifferent isoformsAdrenal chromaffin cellsEndocytosisDynaminVariable loopScission eventsSpecific roleCellsKey roleDomainIsoformsDimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation
Burke C, Lemmon M, Coren B, Engelman D, Stern D. Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation. Oncogene 1997, 14: 687-696. PMID: 9038376, DOI: 10.1038/sj.onc.1200873.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTransmembrane domainEpidermal growth factor receptorSignal transductionWild-type domainSecond-site mutationsPosition 664Dimerization domainGrowth factor receptorTyrosine kinaseGlycophorin AFactor receptorValine substitutionDimerizationMutationsTransductionGlutamic acidDomainWeak dimerizationMutantsKinaseSignalingProteinEGFChimeras
1996
Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity
Zheng J, Cahill S, Lemmon M, Fushman D, Schlessinger J, Cowburn D. Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity. Journal Of Molecular Biology 1996, 255: 14-21. PMID: 8568861, DOI: 10.1006/jmbi.1996.0002.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBlood ProteinsDynaminsGTP PhosphohydrolasesHumansKineticsMagnetic Resonance SpectroscopyModels, MolecularPhosphatidic AcidsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphoproteinsProtein ConformationSequence Homology, Amino AcidSpectrometry, FluorescenceConceptsDynamin PH domainPH domainMembrane associationGTPase activityGuanine nucleotide exchange factorsNucleotide exchange factorsPleckstrin homology domainAcidic phospholipidsBinding of phospholipidsHomology domainExchange factorHuman dynaminGTP hydrolysisDynaminLipid head groupsLigand interactionsGTPaseBinding sitesPhosphatidylinositolSpecific sitesProteinPhospholipidsRelative affinityBindingDomain
1995
Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain
Ferguson K, Lemmon M, Schlessinger J, Sigler P. Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell 1995, 83: 1037-1046. PMID: 8521504, DOI: 10.1016/0092-8674(95)90219-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesBlood ProteinsCrystallography, X-RayInositol 1,4,5-TrisphosphateIsoenzymesMolecular ConformationMolecular Sequence DataPhospholipase C gammaPhosphoproteinsProtein ConformationRatsSequence AlignmentSequence Homology, Amino AcidSpectrinType C PhospholipasesConceptsPleckstrin homology domainHigh-affinity complexHomology domainPH domainPhospholipase C-delta 1C-delta 1Affinity complexHead group specificityMembrane targetingLoss of functionSignaling proteinsDomain foldsMutational changesBtk mutantsRegulatory functionsAmino acidsX-ray crystal structureBeta 2Beta 1/beta 2InositolDomainMutantsComplexesProteinTrisphosphate