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.
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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 |
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