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J Biol Chem, Vol. 274, Issue 11, 6875-6881, March 12, 1999
From the Clusterin is a highly conserved protein which is
expressed at increased levels by many cell types in response to a broad
variety of stress conditions. A genuine physiological function for
clusterin has not yet been established. The results presented here
demonstrate for the first time that clusterin has chaperone-like
activity. At physiological concentrations, clusterin potently protected glutathione S-transferase and catalase from heat-induced
precipitation and
Clusterin Has Chaperone-like Activity Similar to That of Small
Heat Shock Proteins
,
Department of Biological Sciences and
§ Department of Chemistry, The University of Wollongong,
Northfields Avenue, Wollongong, New South Wales 2522, Australia and the
¶ Department of Biochemistry, The University of Sydney, Sydney,
New South Wales 2006, Australia
-lactalbumin and bovine serum albumin from
precipitation induced by reduction with dithiothreitol. Enzyme-linked
immunosorbent assay data showed that clusterin bound preferentially to
heat-stressed glutathione S-transferase and to
dithiothreitol-treated bovine serum albumin and
-lactalbumin.
Size exclusion chromatography and SDS-polyacrylamide gel
electrophoresis analyses showed that clusterin formed high molecular
weight complexes (HMW) with all four proteins tested. Small heat shock
proteins (sHSP) also act in this way to prevent protein precipitation
and protect cells from heat and other stresses. The stoichiometric
subunit molar ratios of clusterin:stressed protein during formation of
HMW complexes (which for the four proteins tested ranged from 1.0:1.3
to 1.0:11) is less than the reported ratios for sHSP-mediated formation
of HMW complexes (1.0:1.0 or greater), indicating that clusterin is a
very efficient chaperone. Our results suggest that clusterin may play a
sHSP-like role in cytoprotection.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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