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Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in re...

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Autores principales: Dyakin, Victor V., Uversky, Vladimir N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998916/
https://www.ncbi.nlm.nih.gov/pubmed/35409047
http://dx.doi.org/10.3390/ijms23073687
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author Dyakin, Victor V.
Uversky, Vladimir N.
author_facet Dyakin, Victor V.
Uversky, Vladimir N.
author_sort Dyakin, Victor V.
collection PubMed
description Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are determined by utilizing the energy stored, transferred, and released, via adenosine triphosphate (ATP). At the protein level, the synthesis of a homochiral polypeptide chain of L-amino acids (L-AAs) represents the first state in the evolution of the dynamic non-equilibrium state of the system. At the next step the non-equilibrium state of a protein-centric system is supported and amended by a broad set of posttranslational modifications (PTMs). The enzymatic phosphorylation, being the most abundant and ATP-driven form of PTMs, illustrates the principal significance of the energy-coupling, in maintaining and reshaping the system. However, the physiological functions of phosphorylation are under the permanent risk of being compromised by spontaneous racemization. Therefore, the major distinct steps in protein-centric aging include the biosynthesis of a polypeptide chain, protein folding assisted by the system of PTMs, and age-dependent spontaneous protein racemization and degradation. To the best of our knowledge, we are the first to pay attention to the biphasic, alternative, and stepwise changes in the conformational entropy of protein folding. The broader view on protein folding, including the impact of spontaneous racemization, will help in the goal-oriented experimental design in the field of chiral proteomics.
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spelling pubmed-89989162022-04-12 Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality Dyakin, Victor V. Uversky, Vladimir N. Int J Mol Sci Review Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are determined by utilizing the energy stored, transferred, and released, via adenosine triphosphate (ATP). At the protein level, the synthesis of a homochiral polypeptide chain of L-amino acids (L-AAs) represents the first state in the evolution of the dynamic non-equilibrium state of the system. At the next step the non-equilibrium state of a protein-centric system is supported and amended by a broad set of posttranslational modifications (PTMs). The enzymatic phosphorylation, being the most abundant and ATP-driven form of PTMs, illustrates the principal significance of the energy-coupling, in maintaining and reshaping the system. However, the physiological functions of phosphorylation are under the permanent risk of being compromised by spontaneous racemization. Therefore, the major distinct steps in protein-centric aging include the biosynthesis of a polypeptide chain, protein folding assisted by the system of PTMs, and age-dependent spontaneous protein racemization and degradation. To the best of our knowledge, we are the first to pay attention to the biphasic, alternative, and stepwise changes in the conformational entropy of protein folding. The broader view on protein folding, including the impact of spontaneous racemization, will help in the goal-oriented experimental design in the field of chiral proteomics. MDPI 2022-03-28 /pmc/articles/PMC8998916/ /pubmed/35409047 http://dx.doi.org/10.3390/ijms23073687 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Dyakin, Victor V.
Uversky, Vladimir N.
Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title_full Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title_fullStr Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title_full_unstemmed Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title_short Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality
title_sort arrow of time, entropy, and protein folding: holistic view on biochirality
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998916/
https://www.ncbi.nlm.nih.gov/pubmed/35409047
http://dx.doi.org/10.3390/ijms23073687
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