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

Journal Article


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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.

Publication Date


  • 2013

Citation


  • Wyatt, A. R., Constantinescu, P., Ecroyd, H., Dobson, C. M., Wilson, M. R., Kumita, J. R. & Yerbury, J. J. (2013). Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms. FEBS Letters, 587 (5), 398-403.

Scopus Eid


  • 2-s2.0-84874192917

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1758&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/745

Has Global Citation Frequency


Number Of Pages


  • 5

Start Page


  • 398

End Page


  • 403

Volume


  • 587

Issue


  • 5

Place Of Publication


  • Netherlands

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.

Publication Date


  • 2013

Citation


  • Wyatt, A. R., Constantinescu, P., Ecroyd, H., Dobson, C. M., Wilson, M. R., Kumita, J. R. & Yerbury, J. J. (2013). Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms. FEBS Letters, 587 (5), 398-403.

Scopus Eid


  • 2-s2.0-84874192917

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1758&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/745

Has Global Citation Frequency


Number Of Pages


  • 5

Start Page


  • 398

End Page


  • 403

Volume


  • 587

Issue


  • 5

Place Of Publication


  • Netherlands