Regulated proteolysis induces aberrant phase transition of biomolecular condensates into aggregates; a protective role for the chaperone Clusterin.
chaperone, Clusterin
intrinsically disoreded
liquid-liquid phase separation
neurodegeneration
prion
β-cleavage
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
07
06
2024
revised:
22
10
2024
accepted:
23
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
30
10
2024
Statut:
aheadofprint
Résumé
Several proteins associated with neurodegenerative diseases, such as the mammalian prion protein (PrP), undergo liquid-liquid phase separation (LLPS), which led to the hypothesis that condensates represent precursors in the formation of neurotoxic protein aggregates. However, the mechanisms that trigger aberrant phase separation are incompletely understood. In prion diseases, protease-resistant and infectious amyloid fibrils are composed of N-terminally truncated PrP, termed C2-PrP. C2-PrP is generated by regulated proteolysis (β-cleavage) of the cellular prion protein (PrP
Identifiants
pubmed: 39476948
pii: S0022-2836(24)00468-6
doi: 10.1016/j.jmb.2024.168839
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
168839Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal of Molecular Biology] and was not involved in the editorial review or the decision to publish this article.