FIGURE 7.

Summary of factors affecting the aggregation propensity of WT and H50Q α-Syn. A, schematic free energy landscape for the elongation of WT and H50Q fibrils, illustrating the observed stabilization of H50Q variant fibrils and the potential stabilization of the transition state. Changes to secondary structure populations within the monomeric ensemble are also indicated, and a fragment of α-Syn H50Q (residues x-y) structure is also shown, modeled in a polyproline II conformation. B, measured changes in residual secondary structure can potentially be used to improve the accuracy of the predicted aggregation profiles of WT (black) and H50Q α-Syn (red) by combining the Zyggregator profiles with the β and polyproline II secondary structure populations, P^beta and P^PP, calculated from experimental chemical shifts (Fig. 6D): Z_i^cs = Z_i^agg(P_i^beta + P_i^PP)/(P^beta + P^PP)_max.