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dc.contributor.authorAprile, Francesco A
dc.contributor.authorArosio, Paolo
dc.contributor.authorFusco, Giuliana
dc.contributor.authorChen, Serene W
dc.contributor.authorKumita, Janet R
dc.contributor.authorDhulesia, Anne
dc.contributor.authorTortora, Paolo
dc.contributor.authorKnowles, Tuomas PJ
dc.contributor.authorVendruscolo, Michele
dc.contributor.authorDobson, Christopher M
dc.contributor.authorCremades, Nunilo
dc.date.accessioned2017-11-13T13:54:07Z
dc.date.available2017-11-13T13:54:07Z
dc.date.issued2017-03-07
dc.identifier.issn0006-2960
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/269003
dc.description.abstractThe Hsp70 family of chaperones plays an essential role in suppressing protein aggregation in the cell. Here we investigate the factors controlling the intrinsic ability of human Hsp70 to inhibit the elongation of amyloid fibrils formed by the Parkinson's disease-related protein α-synuclein. Using kinetic analysis, we show that Hsp70 binds preferentially to α-synuclein fibrils as a consequence of variations in the association and dissociation rate constants of binding to the different aggregated states of the protein. Our findings illustrate the importance of the kinetics of binding of molecular chaperones, and also of potential therapeutic molecules, in the efficient suppression of specific pathogenic events linked to neurodegeneration.
dc.description.sponsorshipBBSRC (BB/J002119/1), European Research Council (337969)
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.subjectBinding, Competitive
dc.subjectHSP70 Heat-Shock Proteins
dc.subjectHumans
dc.subjectKinetics
dc.subjectProtein Multimerization
dc.subjectProtein Structure, Secondary
dc.subjectSubstrate Specificity
dc.subjectalpha-Synuclein
dc.titleInhibition of α-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α-Synuclein Species.
dc.typeArticle
prism.endingPage1180
prism.issueIdentifier9
prism.publicationDate2017
prism.publicationNameBiochemistry
prism.startingPage1177
prism.volume56
dc.identifier.doi10.17863/CAM.10846
dcterms.dateAccepted2017-02-08
rioxxterms.versionofrecord10.1021/acs.biochem.6b01178
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-03-07
dc.contributor.orcidAprile, Francesco [0000-0002-5040-4420]
dc.contributor.orcidKumita, Janet [0000-0002-3887-4964]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.identifier.eissn1520-4995
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Research Council (337969)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/J002119/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/K039520/1)
cam.issuedOnline2017-02-23
rioxxterms.freetoread.startdate2018-02-13


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