Fig. 8

Quaternary structural convergence and secondary autocatalytic pathway at the root of the formation of B_i assemblies. a Different prion strains (S₁, S₂, and S₃) give rise to the formation of common oligomeric assemblies, termed A_i, with a narrowed size distribution during mb-PMCA reactions. This common quaternary structural convergence at the early stage of the replication process suggests the existence of a common conversion pathway and a common oligomerization domain that is independent of the strain structural determinant (SSD, i.e., the PrP domain(s) harboring the replicative and strain information^41,50, represented in red). b A_i and B_i assemblies are in an equilibrium/detailed-balance with their respective suPrP (step I and II) as was previously showed⁴¹ and also demonstrated by the dilution experiment (see Fig. 1e). Based on the constraints imposed by the experimental observations, the best model to account for the cooperative and PrP^C dependency transformation of A_i into B_i assemblies implicates the formation of complex between suPrP^A and suPrP^B (step III). The formation of this complex is at the origin of a secondary templating pathway where the transformation of suPrP^A (A₁) to suPrP^B (B₁) is assisted by suPrP^B, making the process autocatalytic