2021
Cell Boundaries, How Membranes and Their Proteins Work
White S, von Heijne G, Engelman D. Cell Boundaries, How Membranes and Their Proteins Work. 2021 DOI: 10.1201/9780429341328.Peer-Reviewed Original ResearchHigh-resolution micrographsMembrane proteinsMolecular mechanismsOrganization of lipidsBasic physicsWide arrayCell membranePhysicsProteinCentral discoveryBiologyPhysics studentsMembraneBiophysical foundationConcerted useCell boundariesDiscoveryPhysical chemistryAdvanced undergraduateDiagramArrayFoldingOrganizational principlesStructureMicrographs
2011
First Step in Folding of Nonconstitutive Membrane Proteins: Spontaneous Insertion of a Polypeptide into a Lipid Bilayer and Formation of Helical Structure
Karabadzhak A, Weerakkody D, Thakur M, Anderson M, Engelman D, Andreev O, Markin V, Reshetnyak Y. First Step in Folding of Nonconstitutive Membrane Proteins: Spontaneous Insertion of a Polypeptide into a Lipid Bilayer and Formation of Helical Structure. Biophysical Journal 2011, 100: 346a. DOI: 10.1016/j.bpj.2010.12.2088.Peer-Reviewed Original Research
2006
Isolation and Identification of Membrane Protein Oligomers from the E. coli Inner Membrane
Stanley B, Engelman D. Isolation and Identification of Membrane Protein Oligomers from the E. coli Inner Membrane. The FASEB Journal 2006, 20: lb76-lb77. DOI: 10.1096/fasebj.20.5.lb76-d.Peer-Reviewed Original ResearchMembrane protein oligomersMembrane proteinsOligomeric complexesHelical membrane protein structuresNatural bilayersProtein oligomersE. coli inner membraneMembrane protein structuresMembrane protein complexesProtein complex associationsAssembly of proteinsF0 subunitsProtein complexesTransmembrane domainATP synthaseInner membraneFunctional complexProtein movementTransporter complexProtein structureFunctional studiesProtein orientationProteinComplex formationMembrane
2003
Amphipols: polymeric surfactants for membrane biology research
Popot J, Berry E, Charvolin D, Creuzenet C, Ebel C, Engelman D, Flötenmeyer M, Giusti F, Gohon Y, Hervé P, Hong Q, Lakey J, Leonard K, Shuman H, Timmins P, Warschawski D, Zito F, Zoonens M, Pucci B, Tribet C. Amphipols: polymeric surfactants for membrane biology research. Cellular And Molecular Life Sciences 2003, 60: 1559-1574. PMID: 14513831, PMCID: PMC11138540, DOI: 10.1007/s00018-003-3169-6.Peer-Reviewed Original ResearchConceptsMembrane proteinsQuasi-irreversible mannerPolymeric surfactantsAmphiphilic polymersMembrane biologyAqueous solutionTransmembrane surfaceAmphipolsBiology researchDissociating characterPutative usesNative stateSurfactantsNovel familyProteinCurrent knowledgeRapid inactivationNoncovalentDetergentsPolymersBiologyCompoundsComplexesInactivationAbsence
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 stabilityMutagenesisHelical membrane proteins: diversity of functions in the context of simple architecture
Ubarretxena-Belandia I, Engelman D. Helical membrane proteins: diversity of functions in the context of simple architecture. Current Opinion In Structural Biology 2001, 11: 370-376. PMID: 11406389, DOI: 10.1016/s0959-440x(00)00217-7.Peer-Reviewed Original ResearchConceptsHelical membrane proteinsGenome-wide scaleAlpha-helical conformationDiversity of functionsIdentification of motifsMembrane proteinsProtein regionsHelix interactionsPolar sidechainsStructural roleLipid bilayersProteinDiversityMotifUse of deviationsConformationSidechainsFunctionFurther investigationBilayersSequestrationIdentificationConversion of Phospholamban into a Soluble Pentameric Helical Bundle †
Li H, Cocco M, Steitz T, Engelman D. Conversion of Phospholamban into a Soluble Pentameric Helical Bundle †. Biochemistry 2001, 40: 6636-6645. PMID: 11380258, DOI: 10.1021/bi0026573.Peer-Reviewed Original ResearchConceptsMembrane proteinsLipid-exposed surfaceMembrane protein phospholambanLaser lightX-ray scatteringTransmembrane domainHelical bundleWild-type phospholambanOligomeric stateNative phospholambanPolar residuesSimilar foldHydrophobic residuesSoluble proteinReticulum membraneSmall-angle X-ray scatteringHelical pentamersProtein phospholambanSoluble variantProteinNatural proteinsNMR experimentsNative contactsMultiangle laser lightSarcoplasmic reticulum membranesPolar residues drive association of polyleucine transmembrane helices
Zhou F, Merianos H, Brunger A, Engelman D. Polar residues drive association of polyleucine transmembrane helices. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 2250-2255. PMID: 11226225, PMCID: PMC30124, DOI: 10.1073/pnas.041593698.Peer-Reviewed Original ResearchConceptsPolar residuesPolyleucine sequenceHelix associationTransmembrane helix associationInterhelical hydrogen bondingTransmembrane protein functionTransmembrane helicesForm homoProtein functionTransmembrane proteinDrive associationMembrane proteinsDetergent micellesAsparagine residuesGeneral structural featuresBiological membranesResiduesOligomerization specificityProteinSequenceHelixStructural flexibilitySuch interactionsStructural featuresHeterooligomers
2000
Interhelical hydrogen bonding drives strong interactions in membrane proteins
Xiao Zhou F, Cocco M, Russ W, Brunger A, Engelman D. Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nature Structural & Molecular Biology 2000, 7: 154-160. PMID: 10655619, DOI: 10.1038/72430.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAsparagineCell MembraneChloramphenicol O-AcetyltransferaseCircular DichroismDetergentsDimerizationDNA-Binding ProteinsElectrophoresis, Polyacrylamide GelFungal ProteinsGlycophorinsHydrogen BondingLeucine ZippersMagnetic Resonance SpectroscopyMembrane ProteinsMicellesMicrococcal NucleaseMolecular Sequence DataPeptidesProtein ConformationProtein KinasesProtein Structure, SecondaryRecombinant ProteinsSaccharomyces cerevisiae ProteinsConceptsMembrane proteinsHelix associationTransmembrane α-helicesIntegral membrane proteinsInterhelical hydrogen bondingModel transmembrane helixTransmembrane helicesMembrane helicesGCN4 leucine zipperLeucine zipperPolar residuesSoluble proteinHydrophobic leucineΑ-helixBiological membranesProteinHelixNon-specific interactionsValine (HAV) sequenceMembraneZipperFoldingMotifAsparagineResidues
1999
A Method for Determining Transmembrane Helix Association and Orientation in Detergent Micelles Using Small Angle X-Ray Scattering
Bu Z, Engelman D. A Method for Determining Transmembrane Helix Association and Orientation in Detergent Micelles Using Small Angle X-Ray Scattering. Biophysical Journal 1999, 77: 1064-1073. PMID: 10423450, PMCID: PMC1300396, DOI: 10.1016/s0006-3495(99)76956-0.Peer-Reviewed Original ResearchMeSH KeywordsBiophysical PhenomenaBiophysicsButyratesDetergentsDimerizationElectrochemistryGlycophorinsHumansIn Vitro TechniquesMembrane ProteinsMicellesMolecular WeightMutationProtein ConformationProtein Structure, SecondaryQuaternary Ammonium CompoundsRecombinant Fusion ProteinsScattering, RadiationSolutionsSolventsX-RaysConceptsDetergent micellesTransmembrane domainAlpha-helical transmembrane domainsSolution small-angle X-ray scatteringTransmembrane helix associationSolution small-angle X-rayHuman erythrocyte glycophorin ASmall-angle X-ray scatteringMembrane proteinsTransmembrane proteinErythrocyte glycophorin ACarboxyl terminusHelix associationAngle X-ray scatteringGlycophorin AStaphylococcal nucleaseSmall-angle X-rayProteinModel systemMicelle contributionX-ray scatteringAngle X-rayDimerizationGyration analysisN-dodecylTOXCAT: A measure of transmembrane helix association in a biological membrane
Russ W, Engelman D. TOXCAT: A measure of transmembrane helix association in a biological membrane. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 863-868. PMID: 9927659, PMCID: PMC15316, DOI: 10.1073/pnas.96.3.863.Peer-Reviewed Original ResearchMeSH KeywordsATP-Binding Cassette TransportersBacterial ProteinsBase SequenceCarrier ProteinsCell MembraneChloramphenicol O-AcetyltransferaseDNA PrimersDNA-Binding ProteinsEscherichia coliEscherichia coli ProteinsGene LibraryGenes, ReporterGenetic Complementation TestMacromolecular SubstancesMaltose-Binding ProteinsMembrane ProteinsModels, MolecularMolecular Sequence DataMonosaccharide Transport ProteinsPeriplasmic Binding ProteinsProtein FoldingProtein Structure, SecondaryRecombinant Fusion ProteinsSpheroplastsTranscription FactorsConceptsTOXCAT systemDetergent micellesHelical membrane proteinsN-terminal DNATransmembrane helix associationTransmembrane alpha-helixReporter gene encoding chloramphenicolNatural membrane environmentGene encoding chloramphenicolTransmembrane domainTM associationTM dimerizationMembrane proteinsMembrane environmentOligomerization motifPolar residuesAlpha-helixHelix associationSequence specificityChimeric constructsCAT expressionBiological membranesFundamental eventNoncovalent associationAssay distinguishes
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
1997
A Biophysical Study of Integral Membrane Protein Folding †
Hunt J, Earnest T, Bousché O, Kalghatgi K, Reilly K, Horváth C, Rothschild K, Engelman D. A Biophysical Study of Integral Membrane Protein Folding †. Biochemistry 1997, 36: 15156-15176. PMID: 9398244, DOI: 10.1021/bi970146j.Peer-Reviewed Original ResearchConceptsAlpha-helical integral membrane proteinsIntegral membrane proteinsMembrane proteinsIntegral membrane protein foldingMembrane protein foldingNon-native conformationsStable secondary structureCellular chaperonesBiophysical dissectionBeta-sheet structureProtein foldingIndividual polypeptidesBiophysical studiesStructure of bacteriorhodopsinTertiary structureSecondary structureReconstitution protocolsG helicesPolypeptideF helixProteinPhospholipid vesiclesHelixFoldingBacteriorhodopsinSpontaneous, pH-Dependent Membrane Insertion of a Transbilayer α-Helix †
Hunt J, Rath P, Rothschild K, Engelman D. Spontaneous, pH-Dependent Membrane Insertion of a Transbilayer α-Helix †. Biochemistry 1997, 36: 15177-15192. PMID: 9398245, DOI: 10.1021/bi970147b.Peer-Reviewed Original ResearchConceptsLipid bilayersIntegral membrane protein bacteriorhodopsinMembrane-spanning regionIntegral membrane proteinsPH-dependent membrane insertionAspartic acid residuesMembrane protein bacteriorhodopsinInsertion reactionMembrane insertionMembrane proteinsAqueous solutionHydrophobic sequenceAqueous bufferPoor solubilityAlpha-helixAcid residuesSignificant solubilityC-helixSpectroscopic assaysΑ-helixSecondary structureProtein bacteriorhodopsinNeutral pHPeptide associatesBilayersAssessment of the aggregation state of integral membrane proteins in reconstituted phospholipid vesicles using small angle neutron scattering11Edited by M. F. Moody
Hunt J, McCrea P, Zaccaı̈ G, Engelman D. Assessment of the aggregation state of integral membrane proteins in reconstituted phospholipid vesicles using small angle neutron scattering11Edited by M. F. Moody. Journal Of Molecular Biology 1997, 273: 1004-1019. PMID: 9367787, DOI: 10.1006/jmbi.1997.1330.Peer-Reviewed Original ResearchConceptsMembrane protein complexesIntegral membrane proteinsProtein complexesMembrane proteinsIntegral membrane protein complexPhospholipid vesiclesSmall unilamellar phospholipid vesiclesUnilamellar phospholipid vesiclesMolecular massF. MoodySpatial arrangementNon-ionic detergentIndividual complexesVesiclesModel systemMonomeric bacteriorhodopsinProteinUnknown scopeComplexesAggregation stateRadius of gyrationBacteriorhodopsinDetergentsBilayersStructure of the Transmembrane Cysteine Residues in Phospholamban
Arkin I, Adams P, Brünger A, Aimoto S, Engelman D, Smith S. Structure of the Transmembrane Cysteine Residues in Phospholamban. The Journal Of Membrane Biology 1997, 155: 199-206. PMID: 9050443, DOI: 10.1007/s002329900172.Peer-Reviewed Original ResearchConceptsTransmembrane domainCysteine residuesSide chainsPentameric complexCysteine side chainsTransmembrane cysteine residuesLong α-helixIntrahelical hydrogen bondsBackbone carbonyl oxygenSelective ion channelsPolar side chainsElectrostatic potential fieldCarbonyl oxygenSulfhydryl groupsHydrogen bondsMembrane proteinsWild-type phospholambanVibrational spectraMutagenesis studiesTransmembrane peptidesAlanine substitutionsMolecular dynamicsReticulum membraneElectrostatic calculationsΑ-helix
1996
Crossing the Hydrophobic Barrier--Insertion of Membrane Proteins
Engelman D. Crossing the Hydrophobic Barrier--Insertion of Membrane Proteins. Science 1996, 274: 1850-1851. PMID: 8984645, DOI: 10.1126/science.274.5294.1850.Peer-Reviewed Original ResearchFourier transform infrared spectroscopy and site-directed isotope labeling as a probe of local secondary structure in the transmembrane domain of phospholamban
Ludlam C, Arkin I, Liu X, Rothman M, Rath P, Aimoto S, Smith S, Engelman D, Rothschild K. Fourier transform infrared spectroscopy and site-directed isotope labeling as a probe of local secondary structure in the transmembrane domain of phospholamban. Biophysical Journal 1996, 70: 1728-1736. PMID: 8785331, PMCID: PMC1225141, DOI: 10.1016/s0006-3495(96)79735-7.Peer-Reviewed Original ResearchConceptsSite-directed isotope labelingLocal secondary structureIsotope labelingSecondary structureSelective ion channelsTotal reflection Fourier transformPeptide amide groupsAmide IReflection Fourier transformDeuterium/hydrogen exchangeTransmembrane domainMembrane domainsMembrane proteinsTransmembrane orientationAmino acid fragmentSpectroscopic characterizationIon channelsHydrophobic regionAmide carbonylProtein backboneCardiac muscle cellsAmide groupLipid bilayersATPase activityFourier transformMapping the lipid-exposed surfaces of membrane proteins
Arkin I, MacKenzie K, Fisher L, Aimoto S, Engelman D, Smith S. Mapping the lipid-exposed surfaces of membrane proteins. Nature Structural & Molecular Biology 1996, 3: 240-243. PMID: 8605625, DOI: 10.1038/nsb0396-240.Peer-Reviewed Original ResearchConceptsMembrane proteinsLong transmembrane helixLipid-exposed surfaceThree-dimensional foldHigh-resolution structuresRelative rotational orientationTransmembrane helicesTransmembrane segmentsThird cysteineCysteine residuesLipid environmentHelix interfacePentameric complexProteinLipid interfaceStable complexesHelixResiduesUndergoes exchangeSulphydryl groupsPhospholambanComplexesInternal faceCysteineRotational orientationCoassembly of Synthetic Segments of Shaker K+ Channel within Phospholipid Membranes †
Peled-Zehavi H, Arkin I, Engelman D, Shai Y. Coassembly of Synthetic Segments of Shaker K+ Channel within Phospholipid Membranes †. Biochemistry 1996, 35: 6828-6838. PMID: 8639634, DOI: 10.1021/bi952988t.Peer-Reviewed Original ResearchConceptsIntegral membrane proteinsOligomerization of proteinsMembrane-embedded segmentsMembrane-mimetic environmentsAlpha-helical contentAlpha-helical structureLipid/peptide molar ratioS4 regionShaker potassium channelSecondary structure studiesResonance energy transfer measurementsPhospholipid membranesZwitterionic phospholipid vesiclesTransmembrane segmentsMembrane proteinsPhospholipid milieuMimetic environmentsSynthetic segmentsFirst repeatS4 sequenceEel sodium channelS4 segmentEnergy transfer measurementsSecondary structure