Oxidation of proteins: is it a programmed process?

Abstract

Proteins represent extremely susceptible targets for oxidants. Oxidative modifications of proteins may bring about violation of their structure and functionality. It implies that the structures of proteins are not infallible in terms of their antioxidant defence. The protection mechanisms in preventing oxidative damages for proteins within cells are mainly related to a large variety of antioxidant enzymatic systems. In contrast, plasma proteins are scarcely protected by these systems, so the mechanism that provides their functioning in the conditions of generating reactive oxygen species (ROS) seems to be much more complicated. Oxidation of many proteins was long considered as a random process. However, the highly site-specific oxidation processes was convincingly demonstrated for some proteins, indicating that protein structure could be adapted to oxidation. According to our hypothesis, some of the structural elements present in proteins are capable of scavenging ROS to protect other protein structures against ROS toxicity. Various antioxidant elements (distinct subdomains, domains, regions, and polypeptide chains) may act as ROS interceptors, thus mitigating the ROS action on functionally crucial amino acid residues of proteins. In the review, the oxidative modifications of certain plasma proteins, such as α₂-macroglobulin, serum human albumin, fibrinogen, and fibrin-stabilising factor, which differ drastically in their spatial structures and functions, are analysed. The arguments that demonstrate the possibility of existing hypothetical antioxidant structures are presented. For the first time, the emphasis is being placed on the programmed mechanism of protein oxidation.

Keywords:

• Antioxidant defence mechanism
• α₂-macroglobulin
• human serum albumin
• fibrinogen
• fibrin-stabilising factor

Acknowledgements

We would like to take this opportunity to thank all authors, whose outstanding papers cited here have contributed in one way or another to development of the proposed concept about the antioxidant structure of plasma proteins.

Disclosure statement

The authors have declared that there is no conflict of interest.

Additional information

Funding

The study was supported by the Russian Foundation for Basic Research, research projects Nos. 15-04-08188a and 16-34-60244 mol_a_dk.