UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties

Capitini, C; Fani, G; Vega, MV; Penco, A; Canale, C; Cabrita, LD; Calamai, M; ... Chiti, F; + view all (2020) Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties. Amyloid , 28 (1) pp. 56-65. 10.1080/13506129.2020.1826425. Green open access

[thumbnail of Christodoulou_text_31_07_2020.pdf]
Preview
Text
Christodoulou_text_31_07_2020.pdf - Accepted Version

Download (919kB) | Preview

Abstract

Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having amyloid properties. Here we have purified full-length TDP-43 (FL TDP-43) and its C-terminal domain (Ct TDP-43) to investigate the morphological, structural and tinctorial features of aggregates formed in vitro by them at pH 7.4 and 37 °C. AFM images indicate that both protein variants show a tendency to form filaments. Moreover, we show that both FL TDP-43 and Ct TDP-43 filaments possess a largely disordered secondary structure, as ascertained by far-UV circular dichroism and Fourier transform infra-red spectroscopy, do not bind Congo red and induce a very weak increase of thioflavin T fluorescence, indicating the absence of a clear amyloid-like signature.

Type: Article
Title: Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/13506129.2020.1826425
Publisher version: https://doi.org/10.1080/13506129.2020.1826425
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Medicine, General & Internal, Medicine, Research & Experimental, General & Internal Medicine, Research & Experimental Medicine, Motor neuron disease, TDP-43 fibrils, TDP-43 filaments, protein misfolding, protein aggregation, FRONTOTEMPORAL LOBAR DEGENERATION, AMYOTROPHIC-LATERAL-SCLEROSIS, PHASE-SEPARATION, NEURONAL INCLUSIONS, FIBRIL FORMATION, AMYLOID FIBRILS, PROTEIN, AGGREGATION, ALS, FRAGMENTS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10137734
Downloads since deposit
23Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item