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

FEBS Lett. 2013 Mar 1;587(5):398-403. doi: 10.1016/j.febslet.2013.01.020. Epub 2013 Jan 23.


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, the effect of activation on the ability of α(2)M to inhibit amyloid formation by 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 that remain able to degrade polypeptide chains and (ii) by a chaperone action that prevents misfolded clients from continuing along the amyloid forming pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Amyloid / chemistry*
  • Amyloid / ultrastructure
  • Amyloid beta-Peptides / chemistry
  • Benzothiazoles
  • Fluorescent Dyes / chemistry
  • Humans
  • Kinetics
  • Muramidase / chemistry
  • Muramidase / genetics
  • Peptide Fragments / chemistry
  • Protein Multimerization
  • Thiazoles / chemistry
  • Trypsin / chemistry*
  • alpha-Macroglobulins / chemistry*


  • Amyloid
  • Amyloid beta-Peptides
  • Benzothiazoles
  • Fluorescent Dyes
  • Peptide Fragments
  • Thiazoles
  • alpha-Macroglobulins
  • amyloid beta-protein (1-42)
  • thioflavin T
  • Muramidase
  • Trypsin