Homotetrameric enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a model protein for elucidation a capability of the oppositely charged polyelectrolyte to suppress the protein thermoaggregation. Charge density and degree of polymerization of the chains, relative content of GAPDH in the mixture, as well as pH and ionic strength proved to be the factors of the thermoaggregation control. However the electrostatic binding of the most active suppressors, e.g. sodium poly(styrenesulfonate) was attended with marked changes of secondary, tertiary and quaternary structure of GAPDH and clearly defined denaturing. The performed comprehensive study of GAPDH interaction with different tightly bound polysulfoanions revealed the key role of a degree of polymerization and hydrophobicity of the chains in the denaturing, specifically the pronounced adverse effect on the enzyme of relatively hydrophobic short-chained polyanions. Accordingly, the required criteria have been stated as follows: relatively hydrophilic highly polymerized polyelectrolytes that are able to form with a protein of fairly stable water-soluble complexes are best suited to prevent thermoaggregation without drastic change of the protein structure.