Figure 1.

Model of Cu²⁺-dependent amyloid formation of β2m. (a) In the absence of metal, β2m exists as a stable monomer (gray oval). The Cu²⁺ holo form leads to amyloid formation on a timescale of weeks¹⁵. (b) The initial Cu²⁺ binding event is followed by oligomerization on a timescale of ~1 h. The rate-limiting step of this oligomerization is a conformational rearrangement (gray rectangle)¹³. These oligomers require Cu²⁺ for stability and dissociate to monomeric form upon addition of a metal chelate (EDTA). (c) Cu²⁺ acts catalytically, giving rise to chelate-irreversible oligomers in a process that is accelerated by subdenaturing levels of urea comparable to that found in uremic patients²⁸. Chelate resistance persists within the mature fiber.