title: A stretch of residues within the protease-resistant core is not necessary for prion structure and infectivity.
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 PrPCstructure 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 PrPCnor for the formation of a stable prion structure.
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Carola
authors.initials: C
authors.lastname: Munoz-Montesino
authors.affiliation: b Institut de Chimie des Substances Naturelles, CNRS, Université Paris Saclay , Gif-sur-Yvette , France.
authors.forename: Christina
authors.initials: C
authors.lastname: Sizun
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Moudjou
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Herzog
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Reine
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Angelique
authors.initials: A
authors.lastname: Igel-Egalon
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Clément
authors.initials: C
authors.lastname: Barbereau
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chapuis
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Danica
authors.initials: D
authors.lastname: Ciric
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Human
authors.initials: H
authors.lastname: Rezaei
authors.affiliation: a VIM, INRA, Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D051379:Mice; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry* / Q000472:pathogenicity; D011487:Protein Conformation; D014774:Virulence
chemical_list: D011328:Prions
keywords: amino acid deletion; infection; prion disease; structure