Cold destabilization and temperature jump of the murine prion protein mPrP(23–231)

We analyzed the thermal stability of the recombinant murine prion protein mPrP(23–231) with a single tryptophan mutation (F174W) and its perturbation by cold temperature. Compared to the N-terminally truncated ones, full-length construct is significantly unstable and forms intermediate state of urea denaturation, and also undergoes the cold destabilization under the ambient pressure. In order to detect the very early phase of the folding, we also applied a laser-induced temperature jump kinetic measurement and observed a kinetic phase of several microseconds, suggesting the barrierless folding process. The conformational instability and low barriers between different conformers may explain the unusual flexibility leading to the pathogenic conversion and the strain diversity.