Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick
(A) Evolution of PK resistance and templating propensities of different types of PrP assemblies obtained after sequential unfolding and refolding of the parental prion. PrPSc is the native prion; suPrP is the elementary oligomeric PrP subunit; and rfPrP is the refolded conformer formed after the polymerization of suPrP. The process of conversion of suPrP into rfPrP requires a conformational change in the PrP protomer of suPrP (represented here as a sphere) to form infectious and PK-resistant assemblies (represented as stack of torus). (B) The conserved differential proteolytic pattern of rfPrPT1-Ov-21K and rfPrPT2-Ov-19K suggests that their respective suPrPs (represented respectively as yellow and red spheres) exhibit distinct conformations. During the refolding step (C), two modes of organization contribute to the cohesion within PrPSc assemblies. Weak interactions (in blue) are involved in maintaining the overall quaternary structure by stacking suPrPs, when strong interactions are involved in the cohesion of PrP protomers in suPrP oligomers. The weakness of the interactions interlinking suPrP means that PrPSc assembly and disassembly are highly dynamic events, even in the absence of a chaotropic agent, and free suPrP could exist in equilibrium with infectious assemblies.