Model of PrP replicative interaction mechanisms. MillerMichael B. GeogheganJames C. SupattaponeSurachai 2011 <p>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<sup>Sc</sup> seed binds and propagates efficiently with autologous PrP<sup>C</sup> substrate, using PrP<sup>C</sup> polybasic domains (represented by rectangular protrusion) for docking. However, if PrP<sup>C</sup> lacks one or both polybasic domains, PrP<sup>Sc</sup> binds less well and exhibits impaired propagation. If PrP<sup>Sc</sup> molecules lacking polybasic domains can be formed, they can bind and propagate efficiently with an expanded range of PrP<sup>C</sup> substrates. ΔPBD-PrP<sup>Sc</sup> may propagate by a different mechanism than wild-type PrP<sup>Sc</sup>, utilizing different residues (symbolized by round protrusion) of PrP<sup>C</sup> for binding. A neoepitope (round depression) may be exposed in the polybasic mutant PrP<sup>Sc</sup> molecules. Legend: Sc = PrP<sup>Sc</sup>; C = PrP<sup>C</sup>; WT = wild-type. ΔPBD = deletion in polybasic domain; ++ = polybasic domain.</p>