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Article Dans Une Revue Communications Biology Année : 2019

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

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Résumé

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.
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Dates et versions

hal-02317910 , version 1 (26-05-2020)

Licence

Paternité - CC BY 4.0

Identifiants

Citer

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, 2019, 2 (1), pp.1-13. ⟨10.1038/s42003-019-0608-y⟩. ⟨hal-02317910⟩
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