Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders associated with the conversion of a normal (cellular) prion protein, PrPC, into a misfolded isoform, PrPSc. According to the" protein-only hypothesis" PrPSc itself is the infectious TSE pathogen. One of the strongest arguments supporting this hypothesis is the link between inherited prion diseases and mutations in the gene coding for human PrP. Several point mutations leading to familial prion diseases have been identified in PRNP gene but largely still unknown is how these mutations affect the transition of PrPC to PrPSc. Structural studies on PrP variants carrying familial mutations, more prone to spontaneous conversion into the infectious form, may be an important step toward understanding the molecular mechanism at early stages of the disease. In the current study we have determined a high-resolution 3D structure of the truncated recombinant HuPrP (90-231) with the pathological Q212P mutation that is associated with a Gerstmann-Sträussler-Scheinker (GSS) syndrome. The structure of Q212P mutant reveals unique structural features in comparison to the known wild-type PrP structures. The most remarkable differences involve the C-terminal end of the protein and the β2-α2 loop region. The spontaneous generation of PrPSc in familial cases might be due to the disruptions of the hydrophobic core consisting of β2-α2 loop and α3 helix.
|Titolo:||NMR structure of the human prion protein with the pathological Q212P mutation|
|Autori:||Ilc, G; Giachin, G; Biljan, I; Zhukov, I; Legname, Giuseppe; Plavec, J.|
|Titolo del libro:||Magnetic moments in Central Europe : program and book of abstracts, 16-20 March 2011, Tatranská Lomnica, Slovakia|
|Nome editore:||Slovak National NMR Centre : Slovak Chemical Society|
|Data di pubblicazione:||2011|
|Appare nelle tipologie:||4.1 Contribution in Conference proceedings|