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 α-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.

The Intrinsically Disordered Region of GCE Protein Adopts a More Fixed Structure by Interacting With the LBD of the Nuclear Receptor FTZ-F1

“…The covalent addition of oxygen to M alters its hydrophobicity, which may have functional consequences [85]. Importantly, exposed M affect the function and structure of protein since such residues are predisposed to reversible oxidation and reduction reactions [86,87]. Dynamic changes in these modi cations contribute to many important cellular processes or functions in vivo [85].…”

“…In addition, M and C oxidation can perform antioxidant functions, protecting against the modi cation of other important amino acid residues critical for protein activity. In the case of human α2 macroglobulin (hα2M), a broad spectrum protease inhibitor, oxidation of exposed M residue prevents modi cation of the Y residue located in the active center [84,87]. In the case of GCEC sequencing, analysis indicated two oxidized M: M461 (M71 in GCEC) and M639 (M249 in GCEC).…”

The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1

“…The covalent addition of oxygen to M alters its hydrophobicity, which may have functional consequences [82]. Importantly, exposed M affect the function and structure of protein since such residues are predisposed to reversible oxidation and reduction reactions [83,84]. Dynamic changes in these modi cations contribute to many important cellular processes or functions in vivo [82].…”

Peroxide-induced oxidative modification of hemoglobin

“…Действительно, даже при низких концентрациях пероксида водорода окисление βCys93 и βCys112 в конечном итоге приводят к структурному коллапсу Hb. Плазменные белки, как полагают, в определённой мере адаптированы к вредоносному действию АФК благодаря тому, что некоторые из структурных частей белка способны экранировать другие части и ключевые остатки от окислительного повреждения [12]. Это было убедительно продемонстрировано для молекул плазменного фибринстабилизирующего фактора и фибриногена, которые оказались способными функционировать в условиях массивного окисления, так как пост-трансляционные модификации не вовлекали ключевых аминокислотных остатков, ответственных за фукциональность этих белков [5,12].…”