Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification

Mohammed M. Moudjou (1, 2) , Jerome Chapuis (1, 2) , Meriem Mekrouti (1, 2) , Fabienne Reine (1, 2) , Laetitia Herzog (1, 2) , Pierre Sibille (1, 2) , Hubert H. Laude (1, 2) , Didier Vilette (3, 1, 2) , Olivier Andréoletti (3) , Human Rezaei (1, 2) , Michel Dron (1, 2) , Vincent Béringue (1, 2)

1 VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires
2 Université Paris Saclay (COmUE)
3 IHAP - Interactions hôtes-agents pathogènes [Toulouse]

Prions are formed of misfolded assemblies (PrPSc) of the variably N-glycosylated cellular prion protein (PrPC). In infected species, prions replicate by seeding the conversion and polymerization of host PrPC. Distinct prion strains can be recognized, exhibiting defined PrPSc biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrPSc assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrPC glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrPC species of interest as substrate. Applying the technique to PrPC glycosylation mutants expressing cells revealed that neither PrPC nor PrPSc glycoform stoichiometry was instrumental to PrPSc formation and strainness perpetuation. Our study supports the view that strain properties, including PrPSc glycotype are enciphered within PrPSc structural backbone, not in the attached glycans.

Domaines: Sciences du Vivant [q-bio]

Mohammed M. Moudjou, Jerome Chapuis, Meriem Mekrouti, Fabienne Reine, Laetitia Herzog, et al.. Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification. Scientific Reports, 2016, 6, ⟨10.1038/srep29116⟩. ⟨hal-02629949⟩