title: Chaperone-like activity of monomeric human 14-3-3ζ on different protein substrates.
abstract: 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.
authors.affiliation: A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect 33, Moscow 119071, Russian Federation. Electronic address: nikolai.sluchanko@mail.ru.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Sluchanko
authors.affiliation: A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect 33, Moscow 119071, Russian Federation.
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Roman
authors.affiliation: A. N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect 33, Moscow 119071, Russian Federation.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Chebotareva
authors.affiliation: Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation.
authors.forename: Nikolai B
authors.initials: NB
authors.lastname: Gusev
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008274:Magnesium / Q000494:pharmacology; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D009154:Mutation; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D013696:Temperature
chemical_list: D048948:14-3-3 Proteins; D018832:Molecular Chaperones; D008274:Magnesium; D002118:Calcium
keywords: 14-3-3 monomer; Aggregation; Hydrophobicity; Moonlight proteins; Small heat shock proteins; bis-ANS fluorescence