2024
High-resolution yeast actin structures indicate the molecular mechanism of actin filament stiffening by cations
Xu X, Cao W, Swift M, Pandit N, Huehn A, Sindelar C, De La Cruz E, Hanein D, Volkmann N. High-resolution yeast actin structures indicate the molecular mechanism of actin filament stiffening by cations. Communications Chemistry 2024, 7: 164. PMID: 39079963, PMCID: PMC11289367, DOI: 10.1038/s42004-024-01243-x.Peer-Reviewed Original ResearchActin filamentsVertebrate actinsActin structuresDNase I binding loopActin filament assemblyEukaryotic cell functionStructures of wild-typeNear-atomic resolution structuresPotential binding sitesActin subunitsFilament assemblyRegulatory proteinsDNase IA167ActinAdjacent subunitsRegulatory roleMolecular mechanismsVertebratesWild-typeGlutamic acidCell functionFilamentsSubunitResiduesQuantitative correlation of ENPP1 pathogenic variants with disease phenotype
Ansh A, Stabach P, Ciccone C, Cao W, De La Cruz E, Sabbagh Y, Carpenter T, Ferreira C, Braddock D. Quantitative correlation of ENPP1 pathogenic variants with disease phenotype. Bone 2024, 186: 117136. PMID: 38806089, PMCID: PMC11227391, DOI: 10.1016/j.bone.2024.117136.Peer-Reviewed Original ResearchEctonucleotide pyrophosphatase/phosphodiesterase 1Pathogenic variantsDisease phenotypeEnzyme velocityCompound heterozygotesEnzyme activityVariable enzyme activityAutosomal dominant phenotypeHigh-throughput assayAutosomal recessive formInnate immune responseENPP1 variantsDamaging variantsENPP1 deficiencyCole diseaseDominant phenotypeAutosomal dominant diseaseCatalytic velocityRecessive formEnzymePhenotypeWT levelsBio-active moleculesClinical phenotypeDominant diseasePublisher Correction: 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. Publisher Correction: Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex. Nature Communications 2024, 15: 2354. PMID: 38491023, PMCID: PMC10943100, DOI: 10.1038/s41467-024-46804-9.Peer-Reviewed Original ResearchCryo-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 ResearchConceptsArp2/3 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 ResearchConceptsN-terminal regionActin bindingSequence requirementsLIM kinaseAnalysis of individual variantsInactivates cofilinS. cerevisiaeRegulatory tailFamily proteinsActin depolymerizationPhosphorylation sitesKinase recognitionSequence variantsInhibitory phosphorylationCofilinN-terminusIndividual variantsFunctional constraintsActinDisordered sequencesPhosphorylationSequenceBiochemical analysisSequence constraintsKinase
2023
Cofilin-mediated actin filament network flexibility facilitates 2D to 3D actomyosin shape change
Sun Z, Yadav V, Amiri S, Cao W, De La Cruz E, Murrell M. Cofilin-mediated actin filament network flexibility facilitates 2D to 3D actomyosin shape change. European Journal Of Cell Biology 2023, 103: 151379. PMID: 38168598, DOI: 10.1016/j.ejcb.2023.151379.Peer-Reviewed Original ResearchCooperative ligand binding to a double-stranded Ising lattice—Application to cofilin binding to actin filaments
Cao W, Taylor E, De La Cruz E. Cooperative ligand binding to a double-stranded Ising lattice—Application to cofilin binding to actin filaments. PNAS Nexus 2023, 2: pgad331. PMID: 37885622, PMCID: PMC10599439, DOI: 10.1093/pnasnexus/pgad331.Peer-Reviewed Original ResearchExact solutionCluster sizeIsing latticeLattice systemsBest fit parametersTransfer matrix methodInfinite onesChemical physicsMatrix methodCooperative ligandFit parametersLigand binding interactionsLinear polymersAdditional experimental informationBinding interactionsIsingSolutionDouble-stranded modelAnalysis of varietyLigandsElectron microscopyPolymersExperimental informationExperimental observationsPhysicsFriction patterns guide actin network contraction
Colin A, Orhant-Prioux M, Guérin C, Savinov M, Cao W, Vianay B, Scarfone I, Roux A, De La Cruz E, Mogilner A, Théry M, Blanchoin L. Friction patterns guide actin network contraction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300416120. PMID: 37725653, PMCID: PMC10523593, DOI: 10.1073/pnas.2300416120.Peer-Reviewed Original ResearchConceptsFriction forceTwist 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
2022
Flagella-like beating of actin bundles driven by self-organized myosin waves
Pochitaloff M, Miranda M, Richard M, Chaiyasitdhi A, Takagi Y, Cao W, De La Cruz E, Sellers J, Joanny J, Jülicher F, Blanchoin L, Martin P. Flagella-like beating of actin bundles driven by self-organized myosin waves. Nature Physics 2022, 18: 1240-1247. PMID: 37396880, PMCID: PMC10312380, DOI: 10.1038/s41567-022-01688-8.Peer-Reviewed Original ResearchThe nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release
Gray S, Cao W, Montpetit B, De La Cruz EM. The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release. Nucleic Acids Research 2022, 50: 3998-4011. PMID: 35286399, PMCID: PMC9023272, DOI: 10.1093/nar/gkac164.Peer-Reviewed Original ResearchConceptsNuclear pore complexRNA exportDEAD-box protein Dbp5ATPase cycleDbp5's ATPase activityDEAD (Asp-Glu-Ala-Asp) box protein 5Pore complexDbp5ATP bindingATPase cyclingNucleotide stateCytoplasmic faceGle1Pool of ATPADP-PiGene expressionProtein 5Mechanistic understandingNucleoporinsNup159ATPase activityATP dissociationATPPi releasePi release rate
2021
Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway
Ganga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.Peer-Reviewed Original ResearchConceptsIntracellular pathwaysCiliary membrane biogenesisCiliary membrane formationIntracellular ciliogenesis pathwayMDCK cellsPolarized MDCK cellsDistinct molecular requirementsPrimary cilia formExtracellular pathwaysTissue-specific mannerCiliary pocketGTPase domainMembrane biogenesisDistinct functional propertiesCiliary vesiclesAssembly intermediatesCilia formSignal transductionGTP bindingMother centriolePrimary ciliaCiliogenesisDivergent residuesIntracellular ciliaRab34Clusters 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
Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potencyForce 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 actinADPDirectional allosteric regulation of protein filament length
Jermyn AS, Cao W, Elam WA, De La Cruz EM, Lin MM. Directional allosteric regulation of protein filament length. Physical Review E 2020, 101: 032409. PMID: 32290018, PMCID: PMC7758089, DOI: 10.1103/physreve.101.032409.Peer-Reviewed Original ResearchThermal 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 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