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




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