Résumé
The native soluble as well as different aggregated states of recombinant prion proteins are highly sensitive to high pressure. On the one hand, its application to the native α-helical protein induces reversibly a metastable structure that relaxes to amyloid fibrils after prolonged incubation. On the other hand, its application to synthetic prion amyloid fibrils leads to partial disaggregation into native monomers as well as to proto-filaments that have lost several amyloid features. In addition, heat-induced β-sheet prion protein aggregates are dissolved and revert into α-helical monomers by applying high pressure. This profound pressure sensitivity of prion protein structure is explained by large volume differences of the different structural states. Hence, pressure appears as a suitable thermodynamic parameter for exploring the highly complex conformational landscape of prion protein. Its further analysis should help identifying prion protein structural states that are on the pathogenic pathway.