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

Abstract:

α2-Macroglobulin (α2M) is an extracellular chaperone that inhibits amorphous and fibrillar protein aggregation. The reaction of α2M with proteases results in an 'activated' conformation, where the proteases become covalently-linked within the interior of a cage-like structure formed by α2M. This study investigates, the effect of activation on the ability of α2M to inhibit amyloid formation by Aβ1-42 and I59T human lysozyme and shows that protease-activated α2M can act via two distinct mechanisms: (i) by trapping proteases that remain 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: Aβ1-42 and Aβ1-42 bind by fluorescence technology (View interaction)I59T lysozyme and I59T lysozyme bind by light scattering (View interaction)I59T lysozyme and I59T lysozyme bind by fluorescence technology (View interaction)Alpha-lactalbumin and Alpha-lactalbumin bind by fluorescence technology (View interaction)I59T lysozyme and I59T lysozyme bind by electron microscopy (View interaction)Aβ1-42 and Aβ1-42 bind by electron microscopy (View interaction). © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.