Structural characterization of a neurotoxic threonine-rich peptidi corresponding to the human prion protein alpha-2 helical 180-195 segment, and comparison with full length alpha-2 helix-derived peptides

The 173-195 segment corresponding to the helix 2 of the globular prion protein domain is a good candidate to be one of several “spots” of intrinsic structural flexibility, which might induce local destabilization and concur to protein transformation, leading to aggregation-prone conformations. Here we report CD and NMR studies on the 2-helix-derived peptide of maximal length (hPrP[180-195]) that is able to exhibit a regular structure different from the prevalently random arrangement of other 2-helix-derived peptides. This peptide, which has previously been shown to be affected by buffer composition via the ion charge density dependence typical of Hofmeister effects, corresponds to the C-terminal sequence of the cellular prion protein full length 2-helix and includes the highly conserved threonine-rich 188-195 segment.