Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadata

Cited literature [60 references]  Display  Hide  Download

https://hal.umontpellier.fr/hal-02317910
Contributor : Marion Boutin <>
Submitted on : Tuesday, May 26, 2020 - 10:24:47 PM
Last modification on : Tuesday, March 2, 2021 - 3:56:02 PM

File

Communications Biology_Igel-Eg...
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

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⟩

Share

Metrics

Record views

1040

Files downloads

268