Structural dependence of the cellular isoform of prion protein on solvent: Spectroscopic characterization of an intermediate conformation

Using circular dichroism, fluorescence, and infrared spectroscopies, we studied the secondary structure of purified hamster PrPC in the presence of the mild, nonionic detergent octylglucoside. Under these native conditions, PrPC displayed an unexpectedly high beta-sheet component, intermediate between the values previously reported for PrPSc and an isoform of PrPC isolated in a zwitterionic detergent. The structure of PrPC appeared to depend strongly on the detergent and/or phase. Switching from octylglucoside to zwitterion 3-14 drastically modified PrP secondary structure by increasing the alpha-helix while abolishing the beta-sheet component. In contrast, the conformation of PrPC in zwitterion was highly stable, since reverting to octylglucoside did not restore the original native structure. These and other results show that native PrPC in octylglucoside has some of the conformational characteristics that make the protein susceptible to conversion into PrPSc. Most importantly, this is the first study to demonstrate the intrinsic plasticity of the full-length native PrPC isolated from animal brains. (C) 1999 Academic Press.