Physics-Biology interface seminar: Davy Martin


11:00 - 12:00

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Prion replication and structural diversification mechanisms

Davy Martin (INRA Jouy-en-Josas)

Prions are proteinaceous infectious agents responsible for a range of neurodegenerative diseases in animals and humans. Prion particles are assemblies formed from a misfolded, β-sheet rich, aggregation-prone isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Prions replicate by recruiting and converting PrPC into PrPSc. PrPSc is a pleiomorphic protein as different conformations can dictate different disease phenotypes in the same host species. This is the basis of the strain phenomenon in prion diseases. Moreover, recent experimental evidence suggests further structural heterogeneity in PrPSc assemblies within specific prion populations and strains. Still, this diversity is rather seen as a size continuum of assemblies with the same core structure, while analysis of the available experimental data points to the existence of structurally distinct arrangements. The atomic structure of PrPSc has not been elucidated so far, making the underlying mechanistical processes of emergence and coevolution of structurally distinct assemblies difficult to understood. Here, we will present our latest experimental results and replication model providing mechanistic insights into prion structural diversification, a key determinant for prion adaptation and toxicity.

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