Clusterin has chaperone-like activity similar to that of small heat shock proteins

Clusterin is a highly conserved protein which is expressed at increased lev els by many cell types in response to a broad variety of stress conditions. A genuine physiological function for clusterin has not yet been establishe d. The results presented here demonstrate for the first time that clusterin has chaperone-like activity. At physiological concentrations, clusterin po tently protected glutathione S-transferase and catalase from heat-induced p recipitation and alpha-lactalbumin and bovine serum albumin from precipitat ion induced by reduction with dithiothreitol. Enzyme-linked immunosorbent a ssay data showed that clusterin bound preferentially to heat-stressed gluta thione S-transferase and to dithiothreitol-treated bovine serum albumin and alpha-lactalbumin. Size exclusion chromatography and SDS-polyacrylamide ge l electrophoresis analyses showed that clusterin formed high molecular weig ht complexes (HMW) with all four proteins tested. Small heat shock proteins (sHSP) also act in this way to prevent protein precipitation and protect c ells 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 re ported ratios for sHSP-mediated formation of HMW complexes (1.0:1.0 or grea ter), indicating that clusterin is a very efficient chaperone. Our results suggest that clusterin may play a sHSP-like role in cytoprotection.