Figure 1.

Chaperone assisted prion replication. Prion polymers (shown as stacks of rectangles) grow by addition of monomers (shown as ovals) to the ends. Monomers are converted into the prion conformation when they join the polymer. Fragmentation of an individual polymer by chaperone action results in formation of two polymers, each of which can grow and continue the cycle. Hsp70/40 probably acts directly on polymers, facilitating Hsp104 interaction. Hsp104 extracts monomers from the polymers by extruding them through its central channel, which results in destabilization and fragmentation of the polymer. Hsp70/40 might also act where peptide exits Hsp104 to help extrude monomers and assist refolding. Many co-chaperones that are known to regulate Hsp70 influence prion propagation, possibly by affecting this reaction. Chaperones might also influence prion propagation by affecting rate of incorporation of monomers into polymers.