Article
Pathological mutations H187R and E196K facilitate subdomain separation and prion protein conversion by destabilization of the native structure.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 1 Mar 2015
Hadži San, Ondračka Andrej, Jerala Roman, Hafner-Bratkovič Iva
Abstract excerpt
The mechanism of prion protein (PrP) conversion, the key event in prion diseases, is still not understood. We investigated how perturbations of interactions between the subdomains β1-α1-β2 and α2-α3 affect PrP conversion. In vitro fibrillization and biophysical methods were used to relate mouse PrP conversion kinetics to thermodynamic stability. We show that pathologic mutations H187R and E196K destabilize PrP...
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