Chaperone-like activity of monomeric human 14-3-3ζ on different protein substrates

•Chaperone-like activity of dimeric and monomeric 14-3-3ζ was analysed and compared.•14-3-3ζ species differently affect aggregation of used model proteins.•In all cases effect of both 14-3-3ζ is concentration-dependent.•Overall, monomeric 14-3-3ζ is more effective and shows higher surface hydrophobicity.•Dissociation of abundant 14-3-3 may be benefitful to the cell upon stress conditions.

Members of the 14-3-3 protein family interact with hundreds of different, predominantly phosphorylated, proteins. 14-3-3 dimers are prevalent but exist at the equilibrium with the monomers. Our previous studies using the engineered monomeric 14-3-3ζ (14-3-3ζm) showed that 14-3-3ζ monomer retained binding activity towards selected phosphorylated partners and, in addition, it prevented heat-induced aggregation of myosin subfragment 1. Since the chaperone-like activity of 14-3-3 monomers has been insufficiently studied, here we have analyzed the effect of 14-3-3ζm on the aggregation of different model proteins. We found that 14-3-3ζm demonstrated considerable chaperone-like activity by inhibiting the DTT-induced aggregation of insulin and thermally-induced aggregation of alcohol dehydrogenase and phosphorylase kinase. Importantly, the anti-aggregating activity of 14-3-3ζm was concentration-dependent and overall, was more pronounced than that of its dimeric counterpart. In some cases, the chaperone-like effect of 14-3-3ζm was comparable, or even higher, than that of the small heat shock proteins, HspB6 and HspB5. We suggest that 14-3-3s not only can bind and regulate the activity of multiple phosphoproteins, but also possess moonlighting chaperone-like activity, which is especially pronounced in the case of monomeric forms of 14-3-3 which can be present under certain stress conditions.

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