Fibril-like structures in preparations of scrapie prions purified from hamster brain

The ultrastructure and biochemical composition of the scrapie agent, an infectious particle which causes a degenerative disease of the central nervous system in sheep and goats, has remained elusive for decades. Progress in its purification has shown that the infectivity of the agent depends upon a protein(s). The term “prion” was introduced to reflect the unusual molecular characteristics of the infectious agent. In purified fractions highly enriched for the scrapie prion, we have found rod shaped, fibril-like structures. The purified fractions were prepared using two different procedures: one used sarkosyl gel electrophoresis and the other employed sucrose gradient centrifugation. In these same purified fractions we have also identified a protein of molecular weight 27,000 to 30,000. This protein is unique to fractions purified from scrapie infected brains. The biophysical behavior of the scrapie associated protein parallels that observed for the infectious prion: under nondenaturing conditions both the protein and the prion are resistant to degradation by proteases at 37° for 30 min.