2024
Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex
Chavali S, Chou S, Cao W, Pollard T, De La Cruz E, Sindelar C. Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex. Nature Communications 2024, 15: 2059. PMID: 38448439, PMCID: PMC10918085, DOI: 10.1038/s41467-024-46179-x.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin-Related Protein 2-3 ComplexActinsCryoelectron MicroscopyCytoskeletonPhosphatesConceptsArp2/3 complexActin filamentsCryo-EM structureMother filamentDaughter filamentArp2/3 complex nucleates branched actin filamentsActin filament branchingBranched actin filamentsDissociation of PiADP-PiFilament branchingOrganelle movementADP stateBranch junctionsArp3A-resolutionActinArp2/3ADP-BeFxFilamentsADPPhosphate releaseFilament mechanismArp2OrganellesToxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
Hvorecny K, Sladewski T, De La Cruz E, Kollman J, Heaslip A. Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover. Nature Communications 2024, 15: 1840. PMID: 38418447, PMCID: PMC10902351, DOI: 10.1038/s41467-024-46111-3.Peer-Reviewed Original ResearchConceptsActin filamentsDynamic properties of actin filamentsProperties of actin filamentsCytoskeletal protein actinFilamentous actin networkSkeletal muscle actinCryo-EM structureIn vitro assemblyOrganelle inheritanceD-loopActin networkNucleotide exchangeLive cell imagingProteins actinSkeletal actinConserved structureEvolutionary changesActinApicomplexan parasitesAssembly contactsIntracellular parasitesMonomer dissociationApicomplexanFilamentsBiophysical propertiesDistinct functional constraints driving conservation of the cofilin N-terminal regulatory tail
Sexton J, Potchernikov T, Bibeau J, Casanova-Sepúlveda G, Cao W, Lou H, Boggon T, De La Cruz E, Turk B. Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail. Nature Communications 2024, 15: 1426. PMID: 38365893, PMCID: PMC10873347, DOI: 10.1038/s41467-024-45878-9.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActinsCofilin 1HumansLim KinasesPhosphorylationSaccharomyces cerevisiaeConceptsN-terminal regionActin bindingSequence requirementsLIM kinaseAnalysis of individual variantsInactivates cofilinS. cerevisiaeRegulatory tailFamily proteinsActin depolymerizationPhosphorylation sitesKinase recognitionSequence variantsInhibitory phosphorylationCofilinN-terminusIndividual variantsFunctional constraintsActinDisordered sequencesPhosphorylationSequenceBiochemical analysisSequence constraintsKinase
2023
Twist response of actin filaments
Bibeau J, Pandit N, Gray S, Nejad N, Sindelar C, Cao W, De La Cruz E. Twist response of actin filaments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2208536120. PMID: 36656858, PMCID: PMC9942836, DOI: 10.1073/pnas.2208536120.Peer-Reviewed Original Research
2021
Clusters of a Few Bound Cofilins Sever Actin Filaments
Bibeau JP, Gray S, De La Cruz EM. Clusters of a Few Bound Cofilins Sever Actin Filaments. Journal Of Molecular Biology 2021, 433: 166833. PMID: 33524412, PMCID: PMC8689643, DOI: 10.1016/j.jmb.2021.166833.Peer-Reviewed Original ResearchStructural basis of fast- and slow-severing actin–cofilactin boundaries
Hocky GM, Sindelar CV, Cao W, Voth GA, De La Cruz EM. Structural basis of fast- and slow-severing actin–cofilactin boundaries. Journal Of Biological Chemistry 2021, 296: 100337. PMID: 33508320, PMCID: PMC7961102, DOI: 10.1016/j.jbc.2021.100337.Peer-Reviewed Original Research
2020
Force and phosphate release from Arp2/3 complex promote dissociation of actin filament branches
Pandit NG, Cao W, Bibeau J, Johnson-Chavarria EM, Taylor EW, Pollard TD, De La Cruz EM. Force and phosphate release from Arp2/3 complex promote dissociation of actin filament branches. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 13519-13528. PMID: 32461373, PMCID: PMC7306818, DOI: 10.1073/pnas.1911183117.Peer-Reviewed Original ResearchConceptsActin filament branchesArp2/3 complexMother filamentFilament branchesTotal internal reflection fluorescence microscopyEssential cellular functionsMechanical forcesActin filament networkReflection fluorescence microscopyCellular functionsActin networkCell motilityComplex generatesActin filamentsArp2/3Filament networkFluorescence microscopyState 1Branch junctionsState 2FilamentsComplexesPhosphate releaseMuscle actinADPThermal fracture kinetics of heterogeneous semiflexible polymers
Lorenzo AM, De La Cruz EM, Koslover EF. Thermal fracture kinetics of heterogeneous semiflexible polymers. Soft Matter 2020, 16: 2017-2024. PMID: 31996875, PMCID: PMC7047574, DOI: 10.1039/c9sm01637f.Peer-Reviewed Original ResearchStructures 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 ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsAnimalsBinding SitesCryoelectron MicroscopyHumansPhosphorylationProtein BindingRabbitsConceptsFilament 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
2019
Active cargo positioning in antiparallel transport networks
Richard M, Blanch-Mercader C, Ennomani H, Cao W, De La Cruz EM, Joanny JF, Jülicher F, Blanchoin L, Martin P. Active cargo positioning in antiparallel transport networks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 14835-14842. PMID: 31289230, PMCID: PMC6660773, DOI: 10.1073/pnas.1900416116.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsBiological TransportMotionMyosinsSingle Molecule ImagingStochastic ProcessesPlastic Deformation and Fragmentation of Strained Actin Filaments
Schramm AC, Hocky GM, Voth GA, Martiel JL, De La Cruz EM. Plastic Deformation and Fragmentation of Strained Actin Filaments. Biophysical Journal 2019, 117: 453-463. PMID: 31301801, PMCID: PMC6697348, DOI: 10.1016/j.bpj.2019.06.018.Peer-Reviewed Original ResearchRegulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity
Zhang XF, Ajeti V, Tsai N, Fereydooni A, Burns W, Murrell M, De La Cruz EM, Forscher P. Regulation of axon growth by myosin II–dependent mechanocatalysis of cofilin activity. Journal Of Cell Biology 2019, 218: 2329-2349. PMID: 31123185, PMCID: PMC6605792, DOI: 10.1083/jcb.201810054.Peer-Reviewed Original Research
2018
Insights into the Cooperative Nature of ATP Hydrolysis in Actin Filaments
Katkar HH, Davtyan A, Durumeric AEP, Hocky GM, Schramm AC, De La Cruz EM, Voth GA. Insights into the Cooperative Nature of ATP Hydrolysis in Actin Filaments. Biophysical Journal 2018, 115: 1589-1602. PMID: 30249402, PMCID: PMC6260209, DOI: 10.1016/j.bpj.2018.08.034.Peer-Reviewed Original ResearchThe actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments
Huehn A, Cao W, Elam WA, Liu X, De La Cruz EM, Sindelar CV. The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments. Journal Of Biological Chemistry 2018, 293: 5377-5383. PMID: 29463680, PMCID: PMC5900768, DOI: 10.1074/jbc.ac118.001843.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsAnimalsCryoelectron MicroscopyProtein Structure, QuaternaryRabbitsConceptsCofilin-decorated segmentsConformational changesCofilin/ADF proteinsActin-remodeling proteinsBind actin filamentsActin filament interactionsCofilin-induced changesEffects of cofilinCooperative conformational changesProtein occupancyADF proteinsCellular processesCell divisionStructure-based methodsCryo-EMActin segmentsIntracellular transportActin filamentsFilament twistCooperative bindingCofilinTwist changesActinFluorophore labelingSubunits
2017
Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly
Zimmermann D, Homa KE, Hocky GM, Pollard LW, De La Cruz EM, Voth GA, Trybus KM, Kovar DR. Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. Nature Communications 2017, 8: 703. PMID: 28951543, PMCID: PMC5614989, DOI: 10.1038/s41467-017-00445-3.Peer-Reviewed Original ResearchPhosphomimetic S3D cofilin binds but only weakly severs actin filaments
Elam WA, Cao W, Kang H, Huehn A, Hocky GM, Prochniewicz E, Schramm AC, Negrón K, Garcia J, Bonello TT, Gunning PW, Thomas DD, Voth GA, Sindelar CV, De La Cruz EM. Phosphomimetic S3D cofilin binds but only weakly severs actin filaments. Journal Of Biological Chemistry 2017, 292: 19565-19579. PMID: 28939776, PMCID: PMC5712599, DOI: 10.1074/jbc.m117.808378.Peer-Reviewed Original ResearchConceptsActin bindingWild-type cofilinActin filament severingHigh cooperativitySubstitution of serineCofilin bindsActin cytoskeletonProtein cofilinCell divisionSer-3Filament severingAtom molecular dynamics simulationsSubunit interactionsN-terminusCofilinBiological processesActin filamentsTime-resolved phosphorescence anisotropyElectron cryomicroscopyRapid remodelingPhosphorylationSeveringFilament mechanical propertiesActin segmentsFilamentsActin Filament Strain Promotes Severing and Cofilin Dissociation
Schramm AC, Hocky GM, Voth GA, Blanchoin L, Martiel JL, De La Cruz EM. Actin Filament Strain Promotes Severing and Cofilin Dissociation. Biophysical Journal 2017, 112: 2624-2633. PMID: 28636918, PMCID: PMC5479148, DOI: 10.1016/j.bpj.2017.05.016.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActinsCryoelectron MicroscopyElasticityMolecular Dynamics SimulationProtein BindingRotationConceptsContinuum mechanics modelStrain energy distributionMechanical propertiesMechanics modelFilament twistingEnhanced spatial resolutionFilament mechanical propertiesElastic energyTorsional rigidityShape deformationSpatial resolutionContinuum modelTorsional flexibilityFilament bendingCofilactin filamentsDynamics simulationsMolecular dynamics simulationsBucklingCofilin-decorated segmentsDeformationBendingBoundariesEnergy distributionLoadFilament model
2016
Cations 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 flexibilityActin Mechanics and Fragmentation*
De La Cruz EM, Gardel ML. Actin Mechanics and Fragmentation*. Journal Of Biological Chemistry 2015, 290: 17137-17144. PMID: 25957404, PMCID: PMC4498053, DOI: 10.1074/jbc.r115.636472.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsBiomechanical PhenomenaHumansModels, MolecularProtein Structure, Tertiary