151. A stretch of residues within the protease-resistant core is not necessary for prion structure and infectivity.
- Author
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Munoz-Montesino C, Sizun C, Moudjou M, Herzog L, Reine F, Igel-Egalon A, Barbereau C, Chapuis J, Ciric D, Laude H, Béringue V, Rezaei H, and Dron M
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Mice, Models, Molecular, Prions pathogenicity, Protein Conformation, Virulence, Prions chemistry
- Abstract
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 α-helical domain of the correctly folded protein and turns into a β-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 PrP
C 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.- Published
- 2017
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