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  • 1 INRA Virologie et Immunologie Moléculaires (VIM) F-78352 Jouy-en-Josas France F-78352 Jouy-en-Josas France
  • 2 Laboratoire d'Etude des Interactions des Molécules Alimentaires (LEIMA) INRA F-44316 Nantes France F-44316 Nantes France
  • 3 Institut National de la Recherche Agronomique (INRA) UC 806/EA 2703 Muséum National d'Histoire Naturelle Institut de Biologie Physico-Chimique 13, rue P. et M. Curie F-75005 Paris France 13, rue P. et M. Curie F-75005 Paris France
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Abstract  

Well-defined set of sheep PrP polymorphisms at positions 136, 154 and 171 define susceptibility to scrapie, ranging from very high susceptibility observed for V136-R154-Q171 (VRQ) variant to resistance for A136-R154-R171 (ARR).To gain insight into the mechanisms of scrapie susceptibility/resistance, the unfolding pathways of the sheep prion protein variants were analysed by differential scanning calorimetry over a wide range of pH. Thermal unfolding occurs, in the 5.0 to 6.0 pH range, through a reversible one-step process while at pH<4.5 and >6.0 unfolding intermediates are formed, which are stable in the 65–80°C range. The observed differences correlate with ovine susceptibility to scrapie.