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J Biol Chem, Vol. 274, Issue 11, 6875-6881, March 12, 1999

Clusterin Has Chaperone-like Activity Similar to That of Small Heat Shock Proteins

David T. HumphreysDagger , John A. Carver§, Simon B. Easterbrook-Smith, and Mark R. WilsonDagger

From the Dagger  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

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 alpha -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 alpha -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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