Hsp26: a temperature-regulated chaperone

Small heat shock proteins (sHsps) are a conserved protein family, with memb ers found in all organisms analysed so far. Several sHsps have been shown t o exhibit chaperone activity and protect proteins from irreversible aggrega tion lit vitro. Here we show that Hsp26, an sHsp from Saccharomyces cerevis iae, is a temperature-regulated molecular chaperone. Like other sHsps, Hsp2 6 forms large oligomeric complexes, At heat shock temperatures, however, th e 24mer chaperone complex dissociates. Interestingly, chaperone assays perf ormed at different temperatures show that the dissociation of the Hsp26 com plex at heat shock temperatures is a prerequisite for efficient chaperone a ctivity. Binding of non-native proteins to dissociated Hsp26 produces large globular assemblies with a structure that appears to be completely reorgan ized relative to the original Hsp26 oligomers, In this complex one monomer of substrate is bound per Hsp26 dimer, The temperature-dependent dissociati on of the large storage form of Hsp26 into a smaller, active species and th e subsequent re-association to a defined large chaperone-substrate complex represents a novel mechanism for the functional activation of a molecular c haperone.