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Ovine prion protein genetic variants are associated with scrapie susceptibility or resistance: they pave the way to understanding the link between protein structural properties and pathogenesis. The studies developed by INRA teams, in association with other national groups, have brought unexpected informations on the stability and conversion of naturally occurring variants in European sheep breeds. The mechanisms underlying these characteristics were unveiled at the atomic level owing to the crystallographic determination of ovine 3D structure, providing the first experimental insight into the structure of the pathological protein. Unfolding intermediates revealed to be small soluble oligomers, which were purified and displayed neurotoxic effects on primary embryonic neurones. Mutational approaches are currently being developed to identify structural determinants of neuronal death on the one hand, and of prion replication on the other hand.

Lien entre type génétique et résistance des ovins à la Tremblante : une approche structurale et physico-chimique