Model of PrP replicative interaction mechanisms.

This diagram summarizes a proposed model for the interaction, propagation, and infectivity behavior of wild-type and polybasic deletion mutant PrP molecules. Wild-type PrP^Sc seed binds and propagates efficiently with autologous PrP^C substrate, using PrP^C polybasic domains (represented by rectangular protrusion) for docking. However, if PrP^C lacks one or both polybasic domains, PrP^Sc binds less well and exhibits impaired propagation. If PrP^Sc molecules lacking polybasic domains can be formed, they can bind and propagate efficiently with an expanded range of PrP^C substrates. ΔPBD-PrP^Sc may propagate by a different mechanism than wild-type PrP^Sc, utilizing different residues (symbolized by round protrusion) of PrP^C for binding. A neoepitope (round depression) may be exposed in the polybasic mutant PrP^Sc molecules. Legend: Sc = PrP^Sc; C = PrP^C; WT = wild-type. ΔPBD = deletion in polybasic domain; ++ = polybasic domain.