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Structural dissection of amyloid aggregates of TDP-43 and its C-terminal fragments TDP-35 and TDP-16

dc.rights.licenseopenen_US
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorSHENOY, Jayakrishna
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorEL MAMMERI, Nadia
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDUTOUR, Antoine
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBERBON, Melanie
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorSAAD, Ahmad
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLENDS, Alons
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
dc.contributor.authorMORVAN, Estelle
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGRELARD, Axelle
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLECOMTE, Sophie
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
dc.contributor.authorKAUFFMANN, Brice
dc.contributor.authorTHEILLET, Francois-Xavier
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorHABENSTEIN, Birgit
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLOQUET, Antoine
dc.date.accessioned2020-04-22T15:11:06Z
dc.date.available2020-04-22T15:11:06Z
dc.date.issued2019
dc.identifier.issn1742-464Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/4357
dc.description.abstractEnThe TAR DNA-binding protein (TDP-43) self-assembles into prion-like aggregates considered to be the structural hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we use a combination of electron microscopy, X-ray fiber diffraction, Fourier-transform infrared spectroscopy analysis, and solid-state NMR spectroscopy to investigate the molecular organization of different TDP constructs, namely the full-length TDP-43 (1-414), two C-terminal fragments [TDP-35 (90-414) and TDP-16 (267-414)], and a C-terminal truncated fragment (TDP-43 increment GaroS2), in their fibrillar state. Although the different protein constructs exhibit similar fibril morphology and a typical cross-beta signature by X-ray diffraction, solid-state NMR indicates that TDP-43 and TDP-35 share the same polymorphic molecular structure, while TDP-16 encompasses a well-ordered amyloid core. We identified several residues in the so-called C-terminal GaroS2 (368-414) domain that participates in the rigid core of TDP-16 fibrils, underlining its importance during the aggregation process. Our findings demonstrate that C-terminal fragments can adopt a different molecular conformation in isolation or in the context of the full-length assembly, suggesting that the N-terminal domain and RRM domains play an important role in the TDP-43 amyloid transition.
dc.description.sponsorshipAdvanced Materials by Design - ANR-10-IDEX-03-02/10-LABX-0042en_US
dc.description.sponsorshipNanostructures biologiques et synthétiques étudiées par Résonance Magnétique Nucléaire du Solide - ANR-14-CE09-0020en_US
dc.language.isoENen_US
dc.subject.enamyloid
dc.subject.enamyotrophic lateral sclerosis
dc.subject.enfrontotemporal dementia
dc.subject.ensolid-state NMR
dc.subject.enTDP-43
dc.title.enStructural dissection of amyloid aggregates of TDP-43 and its C-terminal fragments TDP-35 and TDP-16
dc.typeArticle de revueen_US
dc.identifier.doi10.1111/febs.15159
dc.subject.halChimie/Matériauxen_US
bordeaux.journalFebs Journalen_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
hal.identifierhal-03182111
hal.version1
hal.date.transferred2021-03-26T09:37:16Z
hal.exporttrue
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