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Mutations in tau protein promote aggregation by favoring extended conformations
| dc.rights.license | open | en_US |
| hal.structure.identifier | Dynamiques Chromatiniennes et Transitions Développementales [ChromDev] | |
| hal.structure.identifier | Institut Européen de Chimie et Biologie [IECB] | |
| dc.contributor.author | POUNOT, Kevin | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| hal.structure.identifier | Institut Européen de Chimie et Biologie [IECB] | |
| dc.contributor.author | PIERSSON, Clara | |
| hal.structure.identifier | University of California [Los Angeles] [UCLA] | |
| dc.contributor.author | GORING, Andrew | |
| hal.structure.identifier | Institut Européen de Chimie et Biologie [IECB] | |
| dc.contributor.author | ROSU, Frédéric | |
| hal.structure.identifier | Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA] | |
| dc.contributor.author | GABELICA, Valérie | |
| hal.structure.identifier | Institut de biologie structurale [IBS - UMR 5075] | |
| dc.contributor.author | WEIK, Martin | |
| hal.structure.identifier | University of California [Santa Barbara] [UC Santa Barbara] | |
| dc.contributor.author | HAN, Songi | |
| hal.structure.identifier | Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie [IECB] | |
| dc.contributor.author | FICHOU, Yann | |
| dc.date.accessioned | 2024-04-17T13:36:44Z | |
| dc.date.available | 2024-04-17T13:36:44Z | |
| dc.date.issued | 2023-12-19 | |
| dc.identifier.issn | 2691-3704 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/199205 | |
| dc.description.abstractEn | Amyloid 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 disease-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 radii 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 the aggregation propensity of IDPs. | |
| dc.language.iso | EN | en_US |
| dc.title.en | Mutations in tau protein promote aggregation by favoring extended conformations | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1021/jacsau.3c00550 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio] | en_US |
| dc.description.sponsorshipEurope | Cofactors at the core of tau prion behavior | en_US |
| bordeaux.journal | JACS Au | en_US |
| bordeaux.page | 92-100 | en_US |
| bordeaux.volume | 4 | en_US |
| bordeaux.hal.laboratories | CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04510750 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=JACS%20Au&rft.date=2023-12-19&rft.volume=4&rft.spage=92-100&rft.epage=92-100&rft.eissn=2691-3704&rft.issn=2691-3704&rft.au=POUNOT,%20Kevin&PIERSSON,%20Clara&GORING,%20Andrew&ROSU,%20Fr%C3%A9d%C3%A9ric&GABELICA,%20Val%C3%A9rie&rft.genre=article |
