Protease activation of alpha2-macroglobulin modulates a chaperone-like action with broad specificity.
French K, Yerbury JJ, Wilson MR.
Protease activation of alpha2-macroglobulin modulates a
chaperone-like action with broad specificity. Biochemistry. 2008 Jan
29;47(4):1176-85. Epub 2008 Jan 3.School of Biological Sciences,
University of Wollongong, Northfields Avenue, Wollongong, NSW 2522,
Australia.
Alpha2-macroglobulin (alpha2M) 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 alpha2M with an exposed binding site for the
low-density lipoprotein receptor, facilitating clearance of
alpha2M/protease complexes from the body. This report establishes
that protease activation also modulates a potent chaperone-like
action of alpha2M that has broad specificity for proteins partly
unfolded as a result of heat or oxidative stress. Protease-mediated
activation of alpha2M abolishes its chaperone-like activity.
However, native alpha2M 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 alpha2M/stressed protein/protease complexes. We
propose that alpha2M 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.
External Link: PMID:
18171086