Abstract

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.

中文翻译：

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应激条件下蛋白质中补充金属结合中心的形成

摘要

在许多蛋白质中，在应激条件下会出现补充金属结合中心。它们被称为异常或非典型站点。这种金属结合后，蛋白质的理化性质发生显着变化，并形成非常稳定的蛋白质聚集体，其中金属充当“交联”剂。蛋白质中的补充金属结合中心通常是由于活性氧和氮物种以及活性羰基化合物引起的翻译后修饰而产生的。由于这些修饰而形成的新化学基团可以充当结合金属离子的配体。特别关注半胱氨酸 SH 基团在补充金属结合中心形成中的作用，因为这些基团是活性物质作用的主要目标。当蛋白质构象发生变化时，由于氨基酸残基的暴露，也可能出现补充的金属结合中心。这种中心的出现通常被认为是一种病理过程。这种单方面的方法不允许获得对该现象的整体看法，忽略了与改变的蛋白质形成金属络合物是在改变的氧化还原条件下调整蛋白质性质、活性和稳定性的一种方法的情况。人们正在积极研究金属在蛋白质聚集中的作用，因为它会导致非膜细胞器、液体冷凝物和固体团聚物的形成。在此类聚集体中发现的一些蛋白质是多种疾病的典型蛋白质，例如阿尔茨海默病和亨廷顿病、肌萎缩侧索硬化症和某些类型的癌症。