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dc.contributor.authorSot, Begoña-
dc.contributor.authorRubio-Muñoz, Alejandra-
dc.contributor.authorLeal-Quintero, Ahudrey-
dc.contributor.authorMartínez-Sabando, Javier-
dc.contributor.authorMarcilla, Miguel-
dc.contributor.authorRoodveldt, Cintia-
dc.contributor.authorValpuesta, José M.-
dc.date.accessioned2018-06-05T10:44:44Z-
dc.date.available2018-06-05T10:44:44Z-
dc.date.issued2017-
dc.identifierdoi: 10.1038/srep40859-
dc.identifiere-issn: 2045-2322-
dc.identifier.citationScientific Reports 7: 40859 (2017)-
dc.identifier.urihttp://hdl.handle.net/10261/165688-
dc.description.abstractThe eukaryotic chaperonin CCT (chaperonin containing TCP-1) uses cavities built into its double-ring structure to encapsulate and to assist folding of a large subset of proteins. CCT can inhibit amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington's disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of α-synuclein A53T, one of the mutants responsible for Parkinson's disease. We evaluated fibrillation blockade in α-synuclein A53T deletion mutants and CCT interactions of full-length A53T in distinct oligomeric states to define an inhibition mechanism specific for α-synuclein. CCT interferes with fibre assembly by interaction of its CCT and CCT 3 subunits with the A53T central hydrophobic region (NAC). This interaction is specific to NAC conformation, as it is produced once soluble α-synuclein A53T oligomers form and blocks the reaction before fibres begin to grow. Finally, we show that this association inhibits α-synuclein A53T oligomer toxicity in neuroblastoma cells. In summary, our results and those for huntingtin suggest that CCT is a general modulator of amyloidogenesis via a specific mechanism.-
dc.description.sponsorshipThis work was supported by grants RYC2011-08746 (to BS), RTC-2015-3309-1 (to CR) and BFU2016-75984 (to JMV) from the Spanish Ministry of Economy, the Bolsa de Investigación L’Oréal-UNESCO 2013 (to BS), CP10/00527 from Spanish Ministry of Health (to CR) and grant S2013/MIT-2807 from the Madrid Regional Government (to JMV).-
dc.publisherNature Publishing Group-
dc.relationMINECO/ICTI2013-2016/BFU2016-75984-P-
dc.relationS2013/MIT-2807/NANOBIOSOMA-
dc.relationMINECO/ICTI2013-2016/RTC-2015-3309-1-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.titleThe chaperonin CCT inhibits assembly of α-synuclein amyloid fibrils by a specific, conformation-dependent interaction-
dc.typeartículo-
dc.relation.publisherversionhttps://doi.org/10.1038/srep40859-
dc.date.updated2018-06-05T10:44:44Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/-
dc.contributor.funderL'Oréal-
dc.contributor.funderUnited Nations Educational, Scientific and Cultural Organization-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderComunidad de Madrid-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/100005243es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100012818es_ES
dc.identifier.pmid28102321-
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