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Clusterin Is An Atp-Independent Chaperone With Very Broad Substrate Specificity That Stabilizes Stressed Proteins In A Folding-Competent State, Stephen Poon, Simon Easterbrook-Smith, Mark Rybchyn, John Carver, Mark Wilson

Mark R Wilson

We recently reported that the ubiquitous, secreted protein clusterin has chaperone activity in vitro [Humphreys et al. (1999) J. Biol. Chem. 274, 6875−6881]. In this study, we demonstrate that clusterin (i) inhibits stress-induced precipitation of a very broad range of structurally divergent protein substrates, (ii) binds irreversibly via an ATP-independent mechanism to stressed proteins to form solubilized high molecular weight complexes, (iii) lacks detectable ATPase activity, (iv) when acting alone, does not effect refolding of stressed proteins in vitro, and (v) stabilizes stressed proteins in a state competent for refolding by heat shock protein 70 (HSP70). Furthermore, we show that, …