Prion

How can a protein such as PrP made by a cellular gene become an infectious agent? Prusiner and associates had found that PrP could exist in two forms, a normal or cellular form (PrP^C) normally expressed at low levels in neurons and other cell types, and an abnormal or scrapie form (PrP^Sc) built up in diseased brain. PrP^C is a cell-surface glycoprotein, the function of which has yet to be established. PrP^C consists of a single polypeptide chain folded into predominantly spiral conformations known as α-helices. These structures give rise to a globular shape that is soluble and can be cleared from the cell by degrading enzymes called proteases.

In contrast, PrP^Sc that has been isolated from diseased brain is rich in an alternative conformation that resembles extended strands. These structures are known as β-sheets. The β-sheet rich PrP^Sc tends to aggregate and is resistant to heat and degradation by proteases. It is assumed that PrP^Sc can initiate the infection process by binding to predominantly-helical PrP^C and converting it into more stable PrP^Sc with β-sheet conformation. This will set off a chain reaction leading to accumulation of large amounts of The illustration on the left is a computer-generated image of a healthy human prion protein. That on the right is a model of the disease-causing prion protein. The blue sections are β-strands, the green are α-helices, and the yellow are the chains connecting these regions. PrP^Sc to levels that result in brain tissue damage. The conformational conversion from α-helices to β-sheets transforms the benign PrP^C into disease-causing PrP^Sc. This model of conformational conversion provides useful insights into the pathogenesis of prion diseases.