title: Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution.
abstract: According to the "protein only" hypothesis, a conformational conversion of the non-pathogenic "cellular" prion isoform into a pathogenic "scrapie" isoform is the fundamental event in the onset of prion diseases. During this pathogenic conversion, helix H1 and two adjacent surface loops L2 and L3 of the normal prion protein are thought to undergo a conformational transition into an extended beta-like structure, which is prompted by interactions with the pre-existing beta-sheet. To get more insight into the interaction between the helix and one of the beta-strands in the partially unfolded prion protein, the solution structure of a synthetic linear peptide spanning helix H1 and beta-strand S2 (residues 142-166 in human numbering) was studied by circular dichroism and nuclear magnetic resonance spectroscopies. We found that, in contrast to many prion fragments studied earlier, this peptide (i) is highly soluble and does not aggregate up to a millimolar concentration range in aqueous medium and (ii) exhibits an intrinsic propensity to a beta-hairpin like conformation at neutral pH. This beta-propensity can be one of the internal driving forces of the molecular rearrangement responsible for the pathogenic conversion of the prion protein.
authors.affiliation: Institut National de la Recherche Agronomique 806, Muséum National d'Histoire Naturelle (EA 2703), Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: S A
authors.initials: SA
authors.lastname: Kozin
authors.forename: G
authors.initials: G
authors.lastname: Bertho
authors.forename: A K
authors.initials: AK
authors.lastname: Mazur
authors.forename: H
authors.initials: H
authors.lastname: Rabesona
authors.forename: J P
authors.initials: JP
authors.lastname: Girault
authors.forename: T
authors.initials: T
authors.lastname: Haertlé
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: P
authors.initials: P
authors.lastname: Debey
authors.forename: G H
authors.initials: GH
authors.lastname: Hoa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012756:Sheep; D012996:Solutions
chemical_list: D010446:Peptide Fragments; D011328:Prions; D012996:Solutions