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Possible Phase Effects in the Dispersion of a Globular Protein in the Temperature Range of the Native State

  • MOLECULAR BIOPHYSICS
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Abstract

A qualitative approach to the mechanism of occurrence of phase transitions and equilibria of various types in the dispersions of a globular protein in the temperature range, where the structural state of the protein is considered native, is proposed. It is assumed that two types of native conformers N and N* are possible, having stability maxima in different temperature ranges, between which there is a reversible structural transition. It is also assumed that there are two types of protein intermediates I and I*, coexisting with conformers N and N* in the corresponding temperature ranges. The issue of finding possible ways of transition from the thermodynamics of (pre)denaturation transitions of protein to the thermodynamics of condensation phase transitions of the entire dispersion as a whole, with the formation of phase boundaries, is discussed. It is assumed that intermediates I and I* can participate in “liquid–liquid” (L–L) phase transitions with the formation of microphases (clusters) from them in metastable equilibrium with the solution phase consisting of native conformers. The onset of phase transitions depends both on the microenvironment of protein macromolecules in the dispersion and on the properties of protein intermediates. On phase diagrams constructed in the coordinates “temperature–entropy” {T, S} and “chemical potential of the conformers–temperature"{μi, T}, the zones of metastable states N ↔ I and N* ↔ I*, the upper and lower critical solution temperatures, and the zone of supercritical phase transitions are determined. The conditions under which the metastable equilibria N ↔ I and N* ↔ I* are the result of phase transitions of an L–L type are discussed. It is established that the maximum stability of the protein is achieved precisely in the region of critical phase transitions. This region is homogeneous and is characterized as a zone of reduced thermodynamic stability of the protein dispersion as a whole.

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Funding

The study was carried out by State Order, project no. FMEN-2022-0006.

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Authors and Affiliations

  1. Institute of Biology, Karelian Research Center, Russian Academy of Sciences, 185910, Petrozavodsk, Russia

    S. P. Rozhkov & A. S. Goryunov

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  1. S. P. Rozhkov
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  2. A. S. Goryunov
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Correspondence to S. P. Rozhkov.

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Translated by E. Puchkov

Abbreviations: PT, phase transitions; N, native; D, denatured; PT L–L, phase transitions liquid–liquid; LCDT, lower critical solution temperature; UCDT, upper critical solution temperature.

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Rozhkov, S.P., Goryunov, A.S. Possible Phase Effects in the Dispersion of a Globular Protein in the Temperature Range of the Native State. BIOPHYSICS 67, 876–883 (2022). https://doi.org/10.1134/S0006350922060215

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  • DOI: https://doi.org/10.1134/S0006350922060215

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