Effect of chemical chaperones on processes of protein aggregation proceeding in different kinetic regimes

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Abstract

The formation and accumulation of protein aggregates adversely affect intracellular processes in a living cell and are a negative factor in the production and storage of protein preparations. Chemical chaperones can prevent protein aggregation, but this property is not universal and depends on the structure of the target protein and the kinetics of its aggregation. In this work, we studied the effect of betaine (Bet) and lysine (Lys) on test systems based on thermal aggregation of muscle glycogen phosphorylase b (Phb) at 48°C, UV-irradiated Phb (UV-Phb) at 37°C and apo-form of Phb (apo-Phb) at 37°C and characterized by the order of aggregation with respect to the protein (n) equal to 0.5, 1 or 2, respectively. Dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation have shown that Bet protects Phb and apo-Phb from aggregation, but accelerates the aggregation of UV-Phb. At the same time, Lys prevents UV-Phb and apo-Phb aggregation, but increases the rate of Phb aggregate formation. The mechanisms of chemical chaperone action on the tertiary and quaternary structures and the kinetics of thermal aggregation of the target proteins are discussed. Comparison of the effect of chemical chaperones on test systems with different kinetic regimes of aggregation provides more complete information about the mechanism of their action.

About the authors

V. V Mikhaylova

Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences

Email: mikhaylova.inbi@inbox.ru
119071 Moscow, Russia

T. B Eronina

Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences

Email: mikhaylova.inbi@inbox.ru
119071 Moscow, Russia

N. A Chebotareva

Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences

Email: mikhaylova.inbi@inbox.ru
119071 Moscow, Russia

B. I Kurganov

Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences

Email: mikhaylova.inbi@inbox.ru
119071 Moscow, Russia

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