A stretch of residues within the protease-resistant core is not necessary for prion structure and infectivity

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Munoz-Montesino, Carola | Sizun, Christina | Moudjou, Mohammed | Herzog, Laetitia | Reine, Fabienne | Egalon, Angelique | Barbereau, Clément | Chapuis, Jérôme | Ciric, Danica | Laude, Hubert | Béringue, Vincent | Rezaei, Human | Dron, Michel

Edité par CCSD ; Taylor & Francis -

Mapping out regions of PrP influencing prion conversion remains a challenging issue complicated by the lack of prion structure. The portion of PrP associated with infectivity contains the -helical domain of the correctly folded protein and turns into a -sheet-rich insoluble core in prions. Deletions performed so far inside this segment essentially prevented the conversion. Recently we found that deletion of the last C-terminal residues of the helix H2 was fully compatible with prion conversion in the RK13-ovPrP cell culture model, using 3 different infecting strains. This was in agreement with preservation of the overall PrPC structure even after removal of up to one-third of this helix. Prions with internal deletion were infectious for cells and mice expressing the wild-type PrP and they retained prion strain-specific characteristics. We thus identified a piece of the prion domain that is neither necessary for the conformational transition of PrPC nor for the formation of a stable prion structure.

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