Destabilization of polar interactions in the prion protein triggers misfolding and oligomerization.

ABSTRACT: The prion protein (PrP) misfolds and oligomerizes at pH 4 in the presence of physiological salt concentrations. Low pH and salt cause structural perturbations in the monomeric prion protein that lead to misfolding and oligomerization. However, the changes in stability within different regions of the PrP prior to oligomerization are poorly understood. In this study, we have characterized the local stability in PrP at high resolution using amide temperature coefficients (T_C ) measured by nuclear magnetic resonance (NMR) spectroscopy. The local stability of PrP was investigated under native as well as oligomerizing conditions. We have also studied the rapidly oligomerizing PrP variant (Q216R) and the protective PrP variant (A6). We report that at low pH, salt destabilizes PrP at se

SUBMITTER: Bhate SH 

PROVIDER: S-EPMC8521284 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature