2021
NMR analysis of a 900K GroEL–GroES complex
Fiaux J, Bertelsen E, Horwich A, Wüthrich K. NMR analysis of a 900K GroEL–GroES complex. 2021, 67-71. DOI: 10.1142/9789811235795_0007.Peer-Reviewed Original ResearchDirect NMR observation of a substrate protein bound to the chaperonin GroEL
Horst R, Bertelsen E, Fiaux J, Wider G, Horwich A, Wüthrich K. Direct NMR observation of a substrate protein bound to the chaperonin GroEL. 2021, 99-104. DOI: 10.1142/9789811235795_0011.Peer-Reviewed Original Research
2020
Chaperonin-assisted protein folding: a chronologue
Horwich AL, Fenton WA. Chaperonin-assisted protein folding: a chronologue. Quarterly Reviews Of Biophysics 2020, 53: e4. PMID: 32070442, DOI: 10.1017/s0033583519000143.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino AcidsAnimalsCarbon DioxideChaperoninsCytosolDimerizationHeat-Shock ProteinsHumansHydrophobic and Hydrophilic InteractionsKineticsMiceMitochondriaMutationNeurosporaProtein ConformationProtein DenaturationProtein FoldingRibonuclease, PancreaticRibulose-Bisphosphate CarboxylaseSurface PropertiesTemperature
2019
Hsp110 mitigates α-synuclein pathology in vivo
Taguchi YV, Gorenberg EL, Nagy M, Thrasher D, Fenton WA, Volpicelli-Daley L, Horwich AL, Chandra SS. Hsp110 mitigates α-synuclein pathology in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24310-24316. PMID: 31685606, PMCID: PMC6883785, DOI: 10.1073/pnas.1903268116.Peer-Reviewed Original ResearchConceptsΑ-synuclein pathologyOverexpression of Hsp110Α-synuclein aggregationPresynaptic protein α-synucleinΑ-synuclein seedsΑ-synuclein oligomersLewy bodiesMouse modelParkinson's diseaseCell culture modelSynaptic proteomeΑ-synucleinProtein α-synucleinPathologyCulture modelDiseaseMammalian cell culture modelsProtein changesOverexpressionVivoHsp110Molecular facilitatorsMiceUnbiased analysisBrain
2017
Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric mice
Thomas EV, Fenton WA, McGrath J, Horwich AL. Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e3139-e3148. PMID: 28348221, PMCID: PMC5393223, DOI: 10.1073/pnas.1701465114.Peer-Reviewed Original ResearchConceptsMotor neuronsChimeric miceSpinal cord motor neuronsCranial nerve motor nucleiDouble fluorescenceMammalian nervous systemMo of ageGray matter oligodendrocytesCytosolic proteinsExtraocular nucleiMotor nucleusSpinal cordNervous systemNeuronsMiceSuperoxide dismutase 1 proteinEight-cell embryosPathogenic proteinsOligodendrocytesDismutase 1 proteinThird chimeraChimeric progenyRecent studiesEGFP chimerasCells
2016
Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice
Hadzipasic M, Ni W, Nagy M, Steenrod N, McGinley MJ, Kaushal A, Thomas E, McCormick DA, Horwich AL. Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e7600-e7609. PMID: 27821773, PMCID: PMC5127366, DOI: 10.1073/pnas.1616832113.Peer-Reviewed Original ResearchConceptsALS miceAmyotrophic lateral sclerosisAcute spinal cord slicesSingle-unit extracellular recordingsWhole-cell patch-clamp recordingsLoss of neuronsMotor neuron lossMotor neuron firingSpinal cord slicesPatch-clamp recordingsHigh-frequency firingStep variabilityLethal neurodegenerative diseaseNeuron lossCord slicesSpinal cordLeg flexorsLateral sclerosisGait variabilityVivo effectsClamp recordingsExtracellular recordingsEMG patternsMutant miceNeuron firing
2015
Structure and Action of Molecular Chaperones, Machines that Assist Protein Folding in the Cell
Gierasch L, Horwich A, Slingsby C, Wickner S, Agard D. Structure and Action of Molecular Chaperones, Machines that Assist Protein Folding in the Cell. Series In Structural Biology 2015, Volume 6 DOI: 10.1142/9927.Peer-Reviewed Original Research
2014
Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS
Hadzipasic M, Tahvildari B, Nagy M, Bian M, Horwich AL, McCormick DA. Selective degeneration of a physiological subtype of spinal motor neuron in mice with SOD1-linked ALS. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16883-16888. PMID: 25385594, PMCID: PMC4250117, DOI: 10.1073/pnas.1419497111.Peer-Reviewed Original ResearchConceptsMN cell bodiesMotor neuronsMo of ageCell bodiesSpinal cordSpinal cord tissue slicesWhole-cell patch-clamp recordingsCell patch-clamp recordingsAdult mouse spinal cordIntrinsic electrophysiologic propertiesTwitch muscleSpinal motor neuronsLower extremity musclesTransgenic mouse modelMouse motor neuronsPatch-clamp recordingsAmyotrophic lateral sclerosisMouse spinal cordSlow-twitch muscleSteady-state firing ratePhysiological subtypesRetrograde tracingAcute slicesExtremity musclesPathophysiologic events
2012
3.10 Chaperones and Protein Folding
Horwich A, Buchner J, Smock R, Gierasch L, Saibil H. 3.10 Chaperones and Protein Folding. 2012, 212-237. DOI: 10.1016/b978-0-12-374920-8.00313-1.Peer-Reviewed Original ResearchSubstrate proteinsMolecular chaperonesSolvent-exposed hydrophobic surfaceSmall heat shock proteinsChaperone-bound proteinsProtein binding domainsNon-native conformationsNon-native statesHeat shock proteinsBinding of ATPSpecialized proteinsProtein foldingChaperonesBinding domainsOligomeric assembliesBiophysical methodsShock proteinsConformational changesPolypeptide chainStress conditionsNative stateProteinCurrent understandingFoldingMultimolecular aggregates
2011
The GroEL/GroES Chaperonin Machine
Horwich A, Saibil H. The GroEL/GroES Chaperonin Machine. 2011, 191-207. DOI: 10.1017/cbo9781139003704.012.Peer-Reviewed Original ResearchChaperonin machinePhage infectionKingdoms of lifeATP-dependent proteinEukaryotic organellesBacterial operonsGroE operonMutant cellsDouble-ring architectureProtein foldingCellular metabolismRing assemblyPhage headOperonIdentical subunitsNative stateBroader roleProteinE. coliGenetic deficiencyBiological actionsParticle assemblyAssemblyEubacteriaGroESGroEL/GroES‐mediated protein folding
Horwich A, Tyagi N, Clare D, Saibil H. GroEL/GroES‐mediated protein folding. The FASEB Journal 2011, 25: 319.3-319.3. DOI: 10.1096/fasebj.25.1_supplement.319.3.Peer-Reviewed Original ResearchProtein foldingGroEL/GroES chaperonin systemGroE chaperonin systemSubstrate protein bindingNon-native speciesChaperonin systemGroEL ringApical domainConformational trajectoryDomain movementsGroES bindingGroESHydrophobic contactsGroELFoldingInitial associationBindingProtein bindingOpen ringCryoEMSpeciesATPDomainNumber of approaches
2008
GroEL‐GroES‐mediated protein folding
Horwich A, Chapman E, Koculi E, Apetri A, Fenton W, Farr G, Horst R, Wüthrich K. GroEL‐GroES‐mediated protein folding. The FASEB Journal 2008, 22: 536.2-536.2. DOI: 10.1096/fasebj.22.1_supplement.536.2.Peer-Reviewed Original Research
2006
GroEL—GroES‐Mediated Protein Folding
Horwich A, Farr G, Fenton W. GroEL—GroES‐Mediated Protein Folding. ChemInform 2006, 37: no-no. DOI: 10.1002/chin.200631298.Peer-Reviewed Original Research
2004
Chaperonins
Horwich A, Fenton W, Farr G. Chaperonins. 2004, 393-398. DOI: 10.1016/b0-12-443710-9/00102-2.Peer-Reviewed Original Research
2003
The Role of ATP in directing chaperonin-mediated polypeptide folding
Horwich A, Fenton W. The Role of ATP in directing chaperonin-mediated polypeptide folding. The Enzymes 2003, 23: 399-xii. DOI: 10.1016/s1874-6047(04)80010-6.Peer-Reviewed Original Research
2002
ATP-bound states of GroEL and GroEL-GroES captured by cryo-EM and single particle image processing
Ranson N, Farr G, Roseman A, Gowen B, Fenton W, Horwich A, Saibil H. ATP-bound states of GroEL and GroEL-GroES captured by cryo-EM and single particle image processing. Acta Crystallographica Section A: Foundations And Advances 2002, 58: c7-c7. DOI: 10.1107/s0108767302085367.Peer-Reviewed Original Research
2001
ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy
Ranson N, Farr G, Roseman A, Gowen B, Fenton W, Horwich A, Saibil H. ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy. Cell 2001, 107: 869-879. PMID: 11779463, DOI: 10.1016/s0092-8674(01)00617-1.Peer-Reviewed Original ResearchConceptsCryo-electron microscopySalt-bridge contactsGroEL ringGroEL-GroESChaperonin GroELSalt bridge interactionsCryo-EMMolecular machinesADP complexGroELATPRing complexBridge interactionEffect of ATPCooperativityOpposite ringIntermediate domainGroESGeneral insightsComplexesPolypeptideDomainBridge contactsStructural modelAffinityProtein folding taking shape
Horwich A, Fenton W, Rapoport T. Protein folding taking shape. EMBO Reports 2001, 2: 1068-1073. PMID: 11743017, PMCID: PMC1084171, DOI: 10.1093/embo-reports/kve253.Peer-Reviewed Original ResearchGroEL/GroES-Mediated Folding of a Protein Too Large to Be Encapsulated
Chaudhuri T, Farr G, Fenton W, Rospert S, Horwich A. GroEL/GroES-Mediated Folding of a Protein Too Large to Be Encapsulated. Cell 2001, 107: 235-246. PMID: 11672530, DOI: 10.1016/s0092-8674(01)00523-2.Peer-Reviewed Original ResearchFolding of malate dehydrogenase inside the GroEL–GroES cavity
Chen J, Walter S, Horwich A, Smith D. Folding of malate dehydrogenase inside the GroEL–GroES cavity. Nature Structural & Molecular Biology 2001, 8: 721-728. PMID: 11473265, DOI: 10.1038/90443.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBinding SitesChaperonin 10Chaperonin 60Chromatography, High Pressure LiquidDeuteriumDimerizationHydrogen BondingKineticsMalate DehydrogenaseMass SpectrometryMitochondria, HeartModels, MolecularPeptide FragmentsProtein BindingProtein DenaturationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiaryProtein SubunitsSwineConceptsMalate dehydrogenaseNonnative substrate proteinGroEL-GroES cavitySubstrate proteinsProductive foldingChaperonin GroELApical domainGroESGroELMechanical unfoldingGlobal destabilizationSecondary structureHydrophilic chamberCentral cavityInitial proteinDeuterium exchangeFoldingProteinATPDehydrogenaseHydrophobic central cavityMass spectrometryOpen ringPolypeptideUnfolding