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Protease activation of α2-Macroglobulin modulates a chaperone-like action with broad specificity

Journal Article


Abstract


  • ñ2-Macroglobulin (ñ2M) is a major human blood glycoprotein best known for its ability to inhibit a broad spectrum of proteases by a unique trapping method. This action induces an activated conformation of ñ2M with an exposed binding site for the low density lipoprotein receptor, facilitating clearance of ñ2M-protease complexes from the body. This report establishes that protease activation also modulates a potent chaperone-like action of ñ2M which has broad specificity for proteins partly unfolded as a result of heat or oxidative stress. Protease-mediated activation of ñ2M abolishes its chaperone-like activity. However, native ñ2M is able to form soluble complexes with stressed proteins and then subsequently become activated by interacting with a protease, providing a potential mechanism for the in vivo clearance of ñ2M/stressed protein/ protease complexes. We propose that ñ2M is a newly discovered and unique member of a small group of abundant extracellular proteins with chaperone properties that patrol extracellular spaces for unfolded/misfolded proteins and facilitate their disposal.

Publication Date


  • 2008

Citation


  • French, K., Yerbury, J. J. & Wilson, M. R. (2008). Protease activation of α2-Macroglobulin modulates a chaperone-like action with broad specificity. Biochemistry, 47 (4), 1176-1185.

Scopus Eid


  • 2-s2.0-38549152772

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/965

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 1176

End Page


  • 1185

Volume


  • 47

Issue


  • 4

Place Of Publication


  • United States

Abstract


  • ñ2-Macroglobulin (ñ2M) is a major human blood glycoprotein best known for its ability to inhibit a broad spectrum of proteases by a unique trapping method. This action induces an activated conformation of ñ2M with an exposed binding site for the low density lipoprotein receptor, facilitating clearance of ñ2M-protease complexes from the body. This report establishes that protease activation also modulates a potent chaperone-like action of ñ2M which has broad specificity for proteins partly unfolded as a result of heat or oxidative stress. Protease-mediated activation of ñ2M abolishes its chaperone-like activity. However, native ñ2M is able to form soluble complexes with stressed proteins and then subsequently become activated by interacting with a protease, providing a potential mechanism for the in vivo clearance of ñ2M/stressed protein/ protease complexes. We propose that ñ2M is a newly discovered and unique member of a small group of abundant extracellular proteins with chaperone properties that patrol extracellular spaces for unfolded/misfolded proteins and facilitate their disposal.

Publication Date


  • 2008

Citation


  • French, K., Yerbury, J. J. & Wilson, M. R. (2008). Protease activation of α2-Macroglobulin modulates a chaperone-like action with broad specificity. Biochemistry, 47 (4), 1176-1185.

Scopus Eid


  • 2-s2.0-38549152772

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/965

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 1176

End Page


  • 1185

Volume


  • 47

Issue


  • 4

Place Of Publication


  • United States