%0 Journal Article
%T Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy
%A Gabriele Giachin
%A Ivana Biljan
%A Gregor Ilc
%A Janez Plavec
%A Giuseppe Legname
%J Molecules
%D 2013
%I MDPI AG
%R 10.3390/molecules18089451
%X The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrP C, into its misfolded and pathogenic isoform, known as prion or PrP Sc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs) and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most ¦Á-helical motifs are replaced by ¦Â-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrP C and cause spontaneous conversion to PrP Sc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify ¡°hot spots¡± in PrP C involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrP C epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research.
%K prion protein
%K prions
%K genetic mutations
%K polymorphisms
%K prion diseases
%K 3D structure
%K NMR spectroscopy
%U http://www.mdpi.com/1420-3049/18/8/9451