Mammalian prions: tolerance to sequence changes-how far?

Muhammad Khalid Salamat, Carola Munoz-Montesino, Mohammed Moudjou, Human Rezaei, Hubert Laude, Vincent Béringue, Michel Dron

Research output: Contribution to journalArticlepeer-review


Upon prion infection, abnormal prion protein (PrP (Sc) ) self-perpetuate by conformational conversion of α-helix-rich PrP (C) into β sheet enriched form, leading to formation and deposition of PrP (Sc) aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrP (Sc) and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region.

Original languageEnglish
Pages (from-to)131-5
Number of pages5
Issue number2
Publication statusPublished - 13 Dec 2012


  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Humans
  • Mammals
  • Molecular Sequence Data
  • Mutation
  • Prion Diseases
  • Prions
  • Protein Conformation
  • Protein Engineering
  • Structure-Activity Relationship


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