2021
Structural 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 actinADPStructures 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
The 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 ResearchConceptsCofilin-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
2016
Architecture and Connectivity Govern Actin Network Contractility
Ennomani H, Letort G, Guérin C, Martiel JL, Cao W, Nédélec F, De La Cruz EM, Théry M, Blanchoin L. Architecture and Connectivity Govern Actin Network Contractility. Current Biology 2016, 26: 616-626. PMID: 26898468, PMCID: PMC4959279, DOI: 10.1016/j.cub.2015.12.069.Peer-Reviewed Original Research
2015
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Communications 2015, 6: 10006. PMID: 26624227, PMCID: PMC4686714, DOI: 10.1038/ncomms10006.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseVascular calcificationArterial calcificationOrphan diseaseCommon diseaseSequelae of diseaseEctopic vascular calcificationInternal elastic laminaPrevent mortalityRenal failureCardiac failureKidney diseaseSubcutaneous administrationRodent modelsAnimal modelsEctopic calcificationVascular wallLarge arteriesElastic laminaDiseaseCalcificationCalciphylaxisDecreased concentrationSclerosisArtery
2012
NPP4 is a procoagulant enzyme on the surface of vascular endothelium
Albright RA, Chang WC, Robert D, Ornstein DL, Cao W, Liu L, Redick ME, Young JI, De La Cruz EM, Braddock DT. NPP4 is a procoagulant enzyme on the surface of vascular endothelium. Blood 2012, 120: 4432-4440. PMID: 22995898, PMCID: PMC4017314, DOI: 10.1182/blood-2012-04-425215.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAdultAnimalsBlood CoagulationCoagulantsCyclic Nucleotide Phosphodiesterases, Type 4Dinucleoside PhosphatesEndothelium, VascularFluorescent Antibody TechniqueHumansHydrolysisIn Vitro TechniquesInsectaPhosphoric Diester HydrolasesPlatelet AggregationPyrophosphatasesTissue DistributionConceptsPlatelet dense granule componentsNucleotide pyrophosphatase/phosphodiesteraseRelease of ADPUncharacterized enzymesPyrophosphatase/phosphodiesteraseGranule componentsEnzymatic basisRapid disaggregationDense granule releasePlatelet aggregationExtracellular spaceAp3AConcentration-dependent mannerEnzymeGranule releaseVascular endotheliumADPProcoagulant enzymeADP receptorActivationAggregationMutantsActin Network Architecture Can Determine Myosin Motor Activity
Reymann AC, Boujemaa-Paterski R, Martiel JL, Guérin C, Cao W, Chin HF, De La Cruz EM, Théry M, Blanchoin L. Actin Network Architecture Can Determine Myosin Motor Activity. Science 2012, 336: 1310-1314. PMID: 22679097, PMCID: PMC3649007, DOI: 10.1126/science.1221708.Peer-Reviewed Original Research
2011
Actin Filament Dynamics in the Actomyosin VI Complex Is Regulated Allosterically by Calcium–Calmodulin Light Chain
Prochniewicz E, Pierre A, McCullough BR, Chin HF, Cao W, Saunders LP, Thomas DD, De La Cruz EM. Actin Filament Dynamics in the Actomyosin VI Complex Is Regulated Allosterically by Calcium–Calmodulin Light Chain. Journal Of Molecular Biology 2011, 413: 584-592. PMID: 21910998, PMCID: PMC3633491, DOI: 10.1016/j.jmb.2011.08.058.Peer-Reviewed Original ResearchConceptsActin filament dynamicsMyosin VIFilament dynamicsMicrosecond dynamicsCaM-dependent mannerCalmodulin light chainsLight chainActin bindingActin filamentsDependent CaMIQ domainCaM-dependent regulationFluorescence microscopyEnzymatic activityTransient phosphorescence anisotropyATP utilizationFinal anisotropyMicrosecond rotational dynamicsPhosphorescence anisotropyMyosinStructural dynamicsAnisotropy decaySuch modulationActinRegulationCofilin-Linked Changes in Actin Filament Flexibility Promote Severing
McCullough BR, Grintsevich EE, Chen CK, Kang H, Hutchison AL, Henn A, Cao W, Suarez C, Martiel JL, Blanchoin L, Reisler E, De La Cruz EM. Cofilin-Linked Changes in Actin Filament Flexibility Promote Severing. Biophysical Journal 2011, 101: 151-159. PMID: 21723825, PMCID: PMC3127193, DOI: 10.1016/j.bpj.2011.05.049.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
2006
Energetics and Kinetics of Cooperative Cofilin–Actin Filament Interactions
Cao W, Goodarzi JP, De La Cruz EM. Energetics and Kinetics of Cooperative Cofilin–Actin Filament Interactions. Journal Of Molecular Biology 2006, 361: 257-267. PMID: 16843490, DOI: 10.1016/j.jmb.2006.06.019.Peer-Reviewed Original Research
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
2004
Investigations of Photolysis and Rebinding Kinetics in Myoglobin Using Proximal Ligand Replacements †
Cao W, Ye X, Sjodin T, Christian J, Demidov A, Berezhna S, Wang W, Barrick D, Sage J, Champion P. Investigations of Photolysis and Rebinding Kinetics in Myoglobin Using Proximal Ligand Replacements †. Biochemistry 2004, 43: 11109-11117. PMID: 15323570, DOI: 10.1021/bi049077g.Peer-Reviewed Original ResearchConceptsCO rebinding kineticsRebinding kineticsDiatomic ligandsRaman spectraH93G myoglobinLigand vibrational modesLaser flash photolysisResonance Raman spectraBind exogenous ligandsWild-type MbCOCO rebinding ratesTime-resolved Raman spectroscopyProximal ligandFlash photolysisGeminate phaseVibrational modesProximal linkageLigandRebinding rateKinetic resultsExogenous ligandsPhotolysisKineticsHemeMbCOProximal and Distal Influences on Ligand Binding Kinetics in Microperoxidase and Heme Model Compounds †
Cao W, Ye X, Georgiev G, Berezhna S, Sjodin T, Demidov A, Wang W, Sage J, Champion P. Proximal and Distal Influences on Ligand Binding Kinetics in Microperoxidase and Heme Model Compounds †. Biochemistry 2004, 43: 7017-7027. PMID: 15170339, DOI: 10.1021/bi0497291.Peer-Reviewed Original ResearchConceptsRebinding kineticsTime-resolved IR measurementsCO docking sitesLaser flash photolysisLigand rebinding kineticsTime-resolved Raman spectraCO rebinding kineticsTime-resolved Raman spectroscopyFe-protoporphyrin IXFlash photolysisGeminate rebindingLigand binding kineticsHeme complexNative myoglobinRaman spectraIR measurementsVibrational modesMicelle-encapsulatedDilution conditionsMicroperoxidaseLigandBinding kineticsKineticsEnergetic significanceConcentration samples
2001
Water Penetration and Binding to Ferric Myoglobin †
Cao W, Christian J, Champion P, Rosca F, Sage J. Water Penetration and Binding to Ferric Myoglobin †. Biochemistry 2001, 40: 5728-5737. PMID: 11341838, DOI: 10.1021/bi010067e.Peer-Reviewed Original ResearchConceptsH2O bindingHeme pocketHydrogen bondsHis-64Heme ironFlash photolysis investigationsPhotodissociation of NOFerric heme proteinsH2O ligandsWater moleculesNO photolysisHorse heart metmyoglobinHeme proteinsCO escapeBound waterRebinding rateSmall moleculesH2OPhotolysisDissociation constantBondsHydrogenHemeMoleculesPhysiological NO concentrations