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Mutations in tau protein promote aggregation by favoring extended conformations

dc.rights.licenseopenen_US
dc.contributor.authorPOUNOT, Kevin
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorPIERSSON, Clara
dc.contributor.authorGORING, Andrew
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
dc.contributor.authorROSU, Frederic
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorGABELICA, Valerie
dc.contributor.authorWEIK, Martin
dc.contributor.authorHAN, Songi
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
dc.contributor.authorFICHOU, Yann
dc.date.accessioned2024-06-03T09:55:49Z
dc.date.available2024-06-03T09:55:49Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/200220
dc.description.abstractEnAmyloid aggregation of the intrinsically disordered protein (IDP) tau is involved in several diseases, called tauopathies. Some tauopathies can be inherited due to mutations in the gene encoding tau, which might favor the formation of tau amyloid fibrils. This work aims at deciphering the mechanisms through which the diseases-associated single point mutations promote amyloid formation. We combined biochemical and biophysical characterization, notably small angle X-ray scattering (SAXS), to study six different FTDP-17 derived mutations. We found that the mutations promote aggregation to different degrees and can modulate tau conformational ensembles, intermolecular interactions and liquid-liquid phase separation propensity. In particular, we found a good correlation between the aggregation lag time of the mutants and their radius of gyration. We show that mutations disfavor intramolecular protein interactions, which in turn favor extended conformations and promote amyloid aggregation. This work proposes a new connection between the structural features of tau monomers and their propensity to aggregate, providing a novel assay to evaluate aggregation propensity of IDPs.
dc.language.isoENen_US
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.subject.enIntrinsically disordered protein
dc.subject.enSAXS
dc.subject.entau protein
dc.subject.enamyloid
dc.subject.enIDP conformation
dc.title.enMutations in tau protein promote aggregation by favoring extended conformations
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2023.05.12.540512en_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]en_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biophysiqueen_US
dc.description.sponsorshipEuropeCofactors at the core of tau prion behavioren_US
bordeaux.hal.laboratoriesCBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.import.sourcehal
hal.identifierhal-04255772
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.subtypePrepublication/Preprinten_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=POUNOT,%20Kevin&PIERSSON,%20Clara&GORING,%20Andrew&ROSU,%20Frederic&GABELICA,%20Valerie&rft.genre=preprint


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