REVIEW: Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions

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Olga V. Kosmachevskaya¹, Natalia N. Novikova², Sergey N. Yakunin², and Alexey F. Topunov^1,a*

¹Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia

²National Research Center “Kurchatov Institute”, 123182 Moscow, Russia

Received August 16, 2023; Revised September 21, 2023; Accepted October 29, 2023

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In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as “cross-linking” agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer’s and Huntington’s diseases, amyotrophic lateral sclerosis, and some types of cancer.

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KEY WORDS: metal-binding centers, oxidative stress, nitrosative stress, carbonyl stress, hemoglobin, albumin, thiols

DOI: 10.1134/S0006297924140104

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