Beta Amyloid~Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms.

α(2)-Macroglobulin (α(2)M) is an extracellular chaperone that inhibits amorphous and fibrillar protein aggregation. The reaction of α(2)M with proteases results in an 'activated' conformation, where the proteases become covalently-linked within the interior of a cage-like structure formed by α(2)M. This study investigates, for the first time, the effect of activation on the ability of α(2)M to inhibit amyloid formation of Aβ(1-42) and I59T human lysozyme and shows that protease-activated α(2)M can act via two distinct mechanisms: (i) by trapping proteases still able to degrade polypeptide chains and (ii) by a chaperone action that prevents misfolded clients from continuing along the amyloid forming pathway. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: A beta 1-42andA beta 1-42bindbyfluorescence technology(View interaction)159T lysozymeand159T lysozymebindbylight scattering(View interaction)159T lysozymeand159T lysozymebindbyfluorescence technology(View interaction)Alpha-lactalbuminandAlpha-lactalbuminbindbyfluorescence technology(View interaction)159T lysozymeand159T lysozymebindbyelectron microscopy(View interaction)A beta 1-42andA beta 1-42bindbyelectron microscopy(View interaction