Met166‐Glu168 residues in human PrP β2‐α2 loop account for evolutionary resistance to prion infection

13 Pág. Centro de Investigación en Sanidad Animal (CISA)
The amino acid sequence of prion protein (PrP) is a key determinant in the transmissibility of prion diseases. While PrP sequence is highly conserved among mammalian species, minor changes in the PrP amino acid sequence may confer alterations in the transmissibility of prion diseases. Classical bovine spongiform encephalopathy (C-BSE) is the only zoonotic prion strain reported to date causing variant Creutzfeldt-Jacob disease (vCJD) in humans, although experimental transmission points to atypical L-BSE and some classical scrapie isolates as also zoonotic. The precise molecular elements in the human PrP sequence that limit the transmissibility of prion strains such as sheep/goat scrapie or cervid chronic wasting disease (CWD) are not well known.
This work was supported by grants from the Spanish Ministerio de Economía y Competitividad [AGL2016-78054-R (AEI/FEDER, UE), AGL2012-37988-C04-04 and RTA2012-00004-00-00 and fellowship BES-2010-040922 to P.A.C.], Fundación La Marató de TV3 (201821-31) and the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (fellowship FPI-SGIT-2015-02 to A.M.M.).