Techniques to elucidate the conformation of prions

Figure 1 Different conformations of the prion protein. In mammals and humans both isoforms of prion protein (PrP) [the cellular isoform (PrPC) and the misfolded isoform (PrPSC)] are encoded by the same gene (I). PrPC is shown in green (II). Under specific conditions PrPC can be transferred into a misfolded and then putatively infectious conformation (PrPSC). Prion strains can adopt different conformations (indicated by different symbols and colors). When a misfolded isoform of the prion protein becomes infectious it is characterized by specific features as incubation period, PrPSC-spreading, PrPSC-deposition and a distinct potential of infection. For structural analyses of misfolded prion proteins several methods are available. While FTIR, NMR and X-ray structure analyses provide information about the secondary structure as well as 3D-structural information (“direct”), limited proteolysis, fluorescence spectroscopy, EPR, H/D-exchange, cross-linking or mutational analyses reveal more “indirect” structural information that is focused on specific residues within the protein. FTIR: Fourier-transform infrared.