Enhanced prion protein stability coupled to DNA recognition and milieu acidification.

The prion protein (PrP) is the major agent involved in the transmissible spongiform encephalopathies (TSEs). Nucleic acids have been reported to bind PrP with high affinity, although the physiopathological roles for recognition are still not clear. In this work we investigate the stability of a soluble, 1:1 complex formed between an 18 base-pair DNA fragment and the full-length murine recombinant prion protein (mrPrP). DNA confers a gain in mrPrP stability against urea and guanidinium denaturation, which is enhanced at lower pHs and in moderate concentrations of NaCl. We discuss the cooperative folding transition coupled to DNA binding and acidification in terms of the possible cellular scenarios found during complex internalization and degradation.