Fig. 7
Proposed mechanism for the first steps of D76N aggregation. Under native conditions both wt and D76N are in equilibrium between low and high-energy conformations. While wt high-energy conformation has a contained aggregation propensity, the D76N excited state is less structured, highly dynamic, and exposes highly aggregation-prone regions shown in orange. Thus, modest energies such as shear forces present in the circulation system are sufficient to further unfold D76N β2m termini (model) destabilizing completely β2m fold and leading to amyloid formation
