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The Effect of Chemical Chaperones on Proteins with Different Aggregation Kinetics

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Abstract

Formation and accumulation of protein aggregates adversely affect intracellular processes in living cells and are negative factors in the production and storage of protein preparations. Chemical chaperones can prevent protein aggregation, but this effect is not universal and depends on the target protein structure and kinetics of its aggregation. We studied the effect of betaine (Bet) and lysine (Lys) on thermal aggregation of muscle glycogen phosphorylase b (Phb) at 48°C (aggregation order, n = 0.5), UV-irradiated Phb (UV-Phb) at 37°C (n = 1), and apo-form of Phb (apo-Phb) at 37°C (n = 2). Using dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation, we have shown that Bet protected Phb and apo-Phb from aggregation, but accelerated the aggregation of UV-Phb. At the same time, Lys prevented UV-Phb and apo-Phb aggregation, but increased the rate of Phb aggregation. The mechanisms of chemical chaperone action on the tertiary and quaternary structures and kinetics of thermal aggregation of the target proteins are discussed. Comparison of the effects of chemical chaperones on the proteins with different aggregation kinetics provides more complete information on the mechanism of their action.

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Abbreviations

apo-Phb :

apo form of glycogen phosphorylase b

AUC:

analytical ultracentrifugation

Bet:

betaine

DLS:

dynamic light scattering

DSC:

differential scanning calorimetry

IS:

ionic strength

Lys:

lysine

Phb :

glycogen phosphorylase b

UV-Phb :

UV-irradiated glycogen phosphorylase b

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Acknowledgments

This paper is dedicated to the memory of our supervisor, Prof. Boris Ivanovich Kurganov (1938-2021). B. I. Kurganov had devoted his scientific career to studying the structure and functions of allosteric enzymes, as well as the processes of their denaturation and aggregation. In recent years, his main area of interest has been the kinetics of protein aggregation and the influence of chemical and protein chaperones on it. B. I. Kurganov developed the approaches for establishing the mechanisms of protein aggregation in various test systems and methods for quantifying and comparing the anti-aggregation activity of chaperones of different nature. The studies carried out under the direction of B. I. Kurganov testify to the successful application of the proposed methods.

Funding

The work was supported by the Russian Science Foundation (project no. 16-14-10055 for V.V.M., T.B.E., N.A.C., B.I.K.) and by the Ministry of Science and Higher Education of the Russian Federation (for V.V.M., T.B.E., N.A.C.).

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Authors and Affiliations

  1. Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Centre, Russian Academy of Sciences, 119071, Moscow, Russia

    Valeriya V. Mikhaylova, Tatiana B. Eronina, Natalia A. Chebotareva & Boris I. Kurganov

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  1. Valeriya V. Mikhaylova
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  2. Tatiana B. Eronina
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  3. Natalia A. Chebotareva
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  4. Boris I. Kurganov
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Contributions

B. I. Kurganov developed the study concept and curated the data; V. V. Mikhaylova, T. B. Eronina, and N. A. Chebotareva performed the experiments and analyzed the data; V. V. Mikhaylova, T. B. Eronina, N. A. Chebotareva, and B. I. Kurganov discussed the study results; V. V. Mikhaylova wrote the article; V. V. Mikhaylova, T. B. Eronina, and N. A. Chebotareva reviewed and edited the manuscript.

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Correspondence to Valeriya V. Mikhaylova.

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The authors declare no conflict of interest. This article does not contain description of studies with human participants or animals performed by any of the authors.

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Mikhaylova, V.V., Eronina, T.B., Chebotareva, N.A. et al. The Effect of Chemical Chaperones on Proteins with Different Aggregation Kinetics. Biochemistry Moscow 88, 1–12 (2023). https://doi.org/10.1134/S0006297923010017

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