title: Modulation of 14-3-3/phosphotarget interaction by physiological concentrations of phosphate and glycerophosphates.
abstract: Molecular mechanisms governing selective binding of a huge number of various phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to 14-3-3 and therefore being present at high intracellular concentration, which undergoes significant changes under physiological conditions, phosphate can theoretically regulate interaction of 14-3-3 with phosphorylated targets. In order to check this hypothesis we analyzed effect of phosphate and other natural abundant anions on interaction of 14-3-3 with phosphorylated human small heat shock protein HspB6 (Hsp20) participating in regulation of different intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2-phosphate at physiologically relevant concentrations (5-15 mM) significantly destabilized complexes formed by 14-3-3ζ and phosphorylated HspB6 (pHspB6), presumably, via direct interaction with the substrate-binding site of 14-3-3. Phosphate also destabilized complexes between pHspB6 and 14-3-3γ or the monomeric mutant form of 14-3-3ζ. Inorganic sulfate and pyrophosphate were less effective in modulation of 14-3-3 interaction with its target protein. The inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration-dependent. It is hypothesized that physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3.
authors: Laboratory of Molecular Organization of Biological Structures, AN Bach Institute of Biochemistry of the Russian Academy of Sciences, Moscow, Russian Federation. nikolai.sluchanko@mail.ru
authors: Nikolai N
authors: NN
authors: Sluchanko
authors: Natalia A
authors: NA
authors: Chebotareva
authors: Nikolai B
authors: NB
authors: Gusev
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D000838:Anions; D002850:Chromatography, Gel; D005994:Glycerophosphates / Q000378:metabolism*; D050886:HSP20 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D048948:14-3-3 Proteins; D000838:Anions; D005994:Glycerophosphates; D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D050505:Mutant Proteins; D010710:Phosphates
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