2020
Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments
Huehn AR, Bibeau JP, Schramm AC, Cao W, De La Cruz EM, Sindelar CV. Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 1478-1484. PMID: 31900364, PMCID: PMC6983403, DOI: 10.1073/pnas.1915987117.Peer-Reviewed Original ResearchConceptsFilament severingActin filamentsSevering activityCofilin/ADF familyActin conformational changesActin filament severingFilament-severing activityCryo-electron microscopy dataSevers actin filamentsWeak severing activityUnique binding modeCofilin clustersActin structuresCofilin bindingCofilin-decorated segmentsCofilinMolecular understandingBarbed endsConformational changesCooperative bindingBinding cooperativityFilament endsPositive cooperativityBinding modesSevering
2018
14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
Karlberg T, Hornyak P, Pinto AF, Milanova S, Ebrahimi M, Lindberg M, Püllen N, Nordström A, Löverli E, Caraballo R, Wong EV, Näreoja K, Thorsell AG, Elofsson M, De La Cruz EM, Björkegren C, Schüler H. 14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface. Nature Communications 2018, 9: 3785. PMID: 30224724, PMCID: PMC6141617, DOI: 10.1038/s41467-018-06194-1.Peer-Reviewed Original Research14-3-3 ProteinsADP Ribose TransferasesBacterial ToxinsBinding SitesCrystallography, X-RayEscherichia coliGTPase-Activating ProteinsHost-Pathogen InteractionsHydrophobic and Hydrophilic InteractionsModels, MolecularMolecular ChaperonesProtein ConformationProtein DomainsPseudomonas aeruginosaSaccharomyces cerevisiae
2016
Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics
Wang B, Boeckel GR, Huynh L, Nguyen L, Cao W, De La Cruz EM, Kaftan EJ, Ehrlich BE. Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics. PLOS ONE 2016, 11: e0161414. PMID: 27575489, PMCID: PMC5004852, DOI: 10.1371/journal.pone.0161414.Peer-Reviewed Original ResearchConceptsNeuronal calcium sensor-1NCS-1Altered cell functionCell linesCalcium-dependent processesCalcium binding proteinNeurological diseasesFunctional changesLevel of expressionDrug potencyProtein expressionCell functionMRNA levelsHuman cell linesRelative expressionMost tissuesCell deathPrevious reportsMouse tissuesDifferent human cell linesCell growthFunctional roleBinding characteristicsFunctional differencesTissueCations Stiffen Actin Filaments by Adhering a Key Structural Element to Adjacent Subunits
Hocky GM, Baker JL, Bradley MJ, Sinitskiy AV, De La Cruz EM, Voth GA. Cations Stiffen Actin Filaments by Adhering a Key Structural Element to Adjacent Subunits. The Journal Of Physical Chemistry B 2016, 120: 4558-4567. PMID: 27146246, PMCID: PMC4959277, DOI: 10.1021/acs.jpcb.6b02741.Peer-Reviewed Original ResearchConceptsActin filamentsRegulatory proteinsD-loopSite-specific mutagenesisSpecific divalent cationsFilament severingStructural bioinformaticsAdjacent subunitsAccessible conformational spaceSubunit conformationActin subunitsKey structural elementsAmino acidsLarge-scale changesConformational spaceSubunitsFilament mechanical propertiesProteinFilamentsDivalent cationsMagnesium ionsMolecular dynamics simulationsConformationSitesCofilin
2015
Metavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments
Durer Z, McGillivary RM, Kang H, Elam WA, Vizcarra CL, Hanein D, De La Cruz EM, Reisler E, Quinlan ME. Metavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments. Journal Of Molecular Biology 2015, 427: 2782-2798. PMID: 26168869, PMCID: PMC4540644, DOI: 10.1016/j.jmb.2015.07.005.Peer-Reviewed Original ResearchConceptsMetavinculin tail domainVinculin tail domainActin filamentsTail domainSevering activityCell-extracellular matrix junctionsF-actinC-terminal tail domainTotal internal reflection fluorescence microscopy experimentsLonger splice isoformsLimited proteolysis experimentsActin filament bundlesFluorescence microscopy experimentsMatrix junctionsSite-directed labelingSplice isoformsAbundant proteinsProteolysis experimentsMuscle cell functionFilament organizationVinculinFilament bundlesInterprotomer contactsCell functionFilament flexibility
2011
Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate
Wu X, Bradley MJ, Cai Y, Kümmel D, De La Cruz EM, Barr FA, Reinisch KM. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 18672-18677. PMID: 22065758, PMCID: PMC3219131, DOI: 10.1073/pnas.1110415108.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBiological TransportCrystallography, X-RayDeath Domain Receptor Signaling Adaptor ProteinsGuanineGuanine Nucleotide Exchange FactorsHumansKineticsNucleotidesProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryRab GTP-Binding ProteinsRab1 GTP-Binding ProteinsConceptsGuanine nucleotide exchange factorsDENN domain proteinsMembrane traffic pathwaysNucleotide exchange factorsGDP-bound formGTP-bound formSwitch regions IHigher eukaryotesRab GTPasesGEF familyEukaryotic cellsTraffic pathwaysExchange factorSwitch INucleotide bindingKey regulatorConformational changesFirst structureNovel insightsRab35ProteinDENND1BEukaryotesRegion IGTPases
2010
Robust processivity of myosin V under off-axis loads
Oguchi Y, Mikhailenko SV, Ohki T, Olivares AO, De La Cruz EM, Ishiwata S. Robust processivity of myosin V under off-axis loads. Nature Chemical Biology 2010, 6: 300-305. PMID: 20228794, PMCID: PMC2917589, DOI: 10.1038/nchembio.322.Peer-Reviewed Original Research
2008
Widely Distributed Residues in Thymosin β4 Are Critical for Actin Binding
Au JK, Olivares AO, Henn A, Cao W, Safer D, De La Cruz EM. Widely Distributed Residues in Thymosin β4 Are Critical for Actin Binding. Biochemistry 2008, 47: 4181-4188. PMID: 18327913, PMCID: PMC2587058, DOI: 10.1021/bi701769u.Peer-Reviewed Original ResearchConceptsActin Binding AffinityActin bindingProline residuesHydrophobic residuesAlanine residuesLysine residuesPro27Thymosin beta4Actin monomersPro29MutagenesisHydrophobic contactsLeu28Slow association rateResiduesLys19Thymosin β4Ile34Tbeta4Lys18Binding affinitiesTwo-step mechanismAssociation ratePro4Cis-trans isomerization
2007
Contributions from All Over
AU JK, DE LA CRUZ EM, SAFER D. Contributions from All Over. Annals Of The New York Academy Of Sciences 2007, 1112: 38-44. PMID: 17468230, DOI: 10.1196/annals.1415.015.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBinding SitesDrug StabilityKineticsModels, MolecularProtein ConformationRabbitsThermodynamicsThymosinConceptsProline residuesActin bindingWild-type complexHydrophobic contactsSite-directed mutagenesisStrong actin bindingHydrophobic residuesAlanine residuesCysteine 374Slow association rateRate of associationResiduesMutantsComplex variesTbeta4Association rateSulfo-1BindingCis-trans isomerizationKinetic basisComplexesPro27Pro29Lys19Mutagenesis
2005
Thermodynamics of Nucleotide Binding to Actomyosin V and VI: A Positive Heat Capacity Change Accompanies Strong ADP Binding †
Robblee JP, Cao W, Henn A, Hannemann DE, De La Cruz EM. Thermodynamics of Nucleotide Binding to Actomyosin V and VI: A Positive Heat Capacity Change Accompanies Strong ADP Binding †. Biochemistry 2005, 44: 10238-10249. PMID: 16042401, DOI: 10.1021/bi050232g.Peer-Reviewed Original ResearchMagnesium, ADP, and Actin Binding Linkage of Myosin V: Evidence for Multiple Myosin V−ADP and Actomyosin V−ADP States †
Hannemann DE, Cao W, Olivares AO, Robblee JP, De La Cruz EM. Magnesium, ADP, and Actin Binding Linkage of Myosin V: Evidence for Multiple Myosin V−ADP and Actomyosin V−ADP States †. Biochemistry 2005, 44: 8826-8840. PMID: 15952789, DOI: 10.1021/bi0473509.Peer-Reviewed Original Research
2002
Kinetic Characterization of the Weak Binding States of Myosin V †
Yengo CM, De La Cruz EM, Safer D, Ostap EM, Sweeney HL. Kinetic Characterization of the Weak Binding States of Myosin V †. Biochemistry 2002, 41: 8508-8517. PMID: 12081502, DOI: 10.1021/bi015969u.Peer-Reviewed Original ResearchActin-induced Closure of the Actin-binding Cleft of Smooth Muscle Myosin*
Yengo CM, De La Cruz EM, Chrin LR, Gaffney DP, Berger CL. Actin-induced Closure of the Actin-binding Cleft of Smooth Muscle Myosin*. Journal Of Biological Chemistry 2002, 277: 24114-24119. PMID: 11959853, DOI: 10.1074/jbc.m111253200.Peer-Reviewed Original Research
2000
Thymosin-β4 Changes the Conformation and Dynamics of Actin Monomers
De La Cruz E, Ostap E, Brundage R, Reddy K, Sweeney H, Safer D. Thymosin-β4 Changes the Conformation and Dynamics of Actin Monomers. Biophysical Journal 2000, 78: 2516-2527. PMID: 10777749, PMCID: PMC1300842, DOI: 10.1016/s0006-3495(00)76797-x.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBinding SitesBiophysical PhenomenaBiophysicsCircular DichroismCross-Linking ReagentsFluorescent DyesHumansIn Vitro TechniquesKineticsMacromolecular SubstancesModels, MolecularMuscle, SkeletalMutagenesis, Site-DirectedNaphthalenesulfonatesOsmotic PressureProtein BindingProtein ConformationRabbitsRecombinant ProteinsThermodynamicsThymosinTritiumViscosityConceptsActin monomersActin monomer poolMgATP-actinMetazoan cellsNucleotide exchangeC-terminusSubdomain 2Conformational changesMonomer poolN-iodoacetyl-N'Cleavage siteActinThymosin β4Rate of dissociationAmide protonsSulfo-1Unique abilityBindingStructural dynamicsConformationTerminusNucleotidesProteolysisDifferent stabilitiesDegrees C