Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms.
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Peer-reviewed
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Abstract
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.
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Keywords
Amino Acid Substitution, Amyloid, Amyloid beta-Peptides, Benzothiazoles, Fluorescent Dyes, Humans, Kinetics, Muramidase, Peptide Fragments, Protein Multimerization, Thiazoles, Trypsin, alpha-Macroglobulins
Journal Title
FEBS Lett
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Journal ISSN
0014-5793
1873-3468
1873-3468
Volume Title
587
Publisher
Wiley
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Sponsorship
Biotechnology and Biological Sciences Research Council (BB/E019927/1)