Abstract
Pathogenic prion proteins (PrP^Sc^) are thought to be produced by α‐helical to β‐sheet conformational changes in the normal cellular prion proteins (PrP^C^) located solely in the caveolar compartments. In order to inquire into the possible conformational changes due to the influences of hydrophobic environments within caveolae, the secondary structures of prion protein peptides were studied in various kinds of detergents by CD spectra. The peptides studied were PrP(129–154) and PrP(192–213); the former is supposed to assume β‐sheets and the latter α‐helices, in PrP^Sc^. The secondary structure analyses for the CD spectra revealed that in buffer solutions, both PrP(129–154) and PrP(192–213) mainly adopted random‐coils (∼60%), followed by β‐sheets (30%–40%). PrP(129–154) showed no changes in the secondary structures even in various kinds of detergents such as octyl‐β‐D‐glucopyranoside (OG), octy‐β‐D‐maltopyranoside (OM), sodium dodecyl sulfate (SDS), Zwittergent 3–14 (ZW) and dodecylphosphocholine (DPC). In contrast, PrP(192–213) changed its secondary structure depending on the concentration of the detergents. SDS, ZW, OG and OM increased the α‐helical content, and decreased the β‐sheet and random‐coil contents. DPC also increased the α‐helical content, but to a lesser extent than did SDS, ZW, OG or OM. These results indicate that PrP(129–154) has a propensity to adopt predominantly β‐sheets. On the other hand, PrP(192–213) has a rather fickle propensity and varies its secondary structure depending on the environmental conditions. It is considered that the hydrophobic environments provided by these detergents may mimic those provided by gangliosides in caveolae, the head groups of which consist of oligosaccharide chains containing sialic acids. It is concluded that PrP^C^ could be converted into a nascent PrP^Sc^ having a transient PrP^Sc^ like structure under the hydrophobic environments produced by gangliosides. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.