Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Early stage prion assembly involves two subpopulations with different quaternary structures and a secondary templating pathway

Abstract : The dynamics of aggregation and structural diversification of misfolded, host-encoded proteins in neurodegenerative diseases are poorly understood. In many of these disorders, including Alzheimer’s, Parkinson’s and prion diseases, the misfolded proteins are self-organized into conformationally distinct assemblies or strains. The existence of intrastrain structural heterogeneity is increasingly recognized. However, the underlying processes of emergence and coevolution of structurally distinct assemblies are not mechanistically understood. Here, we show that early prion replication generates two subsets of structurally different assemblies by two sequential processes of formation, regardless of the strain considered. The first process corresponds to a quaternary structural convergence, by reducing the parental strain polydispersity to generate small oligomers. The second process transforms these oligomers into larger ones, by a secondary autocatalytic templating pathway requiring the prion protein. This pathway provides mechanistic insights into prion structural diversification, a key determinant for prion adaptation and toxicity.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [60 références]  Voir  Masquer  Télécharger

https://hal.umontpellier.fr/hal-02317910
Contributeur : Marion Boutin <>
Soumis le : mardi 26 mai 2020 - 22:24:47
Dernière modification le : mercredi 14 octobre 2020 - 04:15:43

Fichier

Communications Biology_Igel-Eg...
Fichiers éditeurs autorisés sur une archive ouverte

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

Angélique Igel-Egalon, Florent Laferrière, Mohammed Moudjou, Jan Bohl, Mathieu Mezache, et al.. Early stage prion assembly involves two subpopulations with different quaternary structures and a secondary templating pathway. Communications Biology, Nature Publishing Group, 2019, 2 (1), pp.1-13. ⟨10.1038/s42003-019-0608-y⟩. ⟨hal-02317910⟩

Partager

Métriques

Consultations de la notice

687

Téléchargements de fichiers

164