Abstract—

Haptoglobin (Hp) is a glycoprotein that binds free hemoglobin (Hb) in plasma and plays a critical role in tissue protection and prevention of oxidative damage. Besides, it has some regulatory functions. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. The human Нр gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of haptoglobin: homozygous Нр1-1 and Нр2-2, and heterozygous Нр2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual predisposition of a person to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting off the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the β-chain of Hp has become the main direction in the study of pathological processes, including malignant neoplasms. These characteristics indicate the possibility of the existence of Hp in the form of a multitude of proteoforms, probably performing different functions. This review is devoted to the description of the structural and functional diversity and the potential use of Hp as a biomarker of various pathologies.

中文翻译：

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结合珠蛋白作为生物标志物

摘要—

结合珠蛋白 (Hp) 是一种糖蛋白，可与血浆中的游离血红蛋白 (Hb) 结合，在组织保护和防止氧化损伤方面发挥关键作用。此外，它还具有一定的调节功能。结合珠蛋白是一种急性期蛋白，其血浆浓度会发生病理变化，对其浓度的检测是正常临床实践的一部分。触珠蛋白是一种主要在肝脏和肺中合成的保守蛋白，是许多疾病（包括各种形式的恶性肿瘤）的潜在生物标志物的研究对象。触珠蛋白具有几个独特的生物物理特性。人类Нр基因是多态性的，具有三个控制触珠蛋白三种主要表型合成的结构等位基因：纯合子 Нр1-1 和 Нр2-2，以及杂合子 Нр2-1，由遗传的等位基因变异组合决定。大量研究表明，触珠蛋白的表型可以用来判断一个人对各种疾病的个体易感性。此外，Hp 还经历了各种翻译后修饰 (PTM)。这些是结构转变（信号肽的去除，将 Pre-Hp 前体分子切断为两个亚基，α 和 β，α 链的有限蛋白水解，二硫键的形成，多聚化），以及 α- 的化学修饰链和 β 链的糖基化。结合珠蛋白 β 链在四个 Asn 位点的糖基化是调节糖蛋白结构和功能的最重要的可变 PTM。Hpβ链修饰寡糖的研究已成为包括恶性肿瘤在内的病理过程研究的主要方向。这些特征表明 Hp 可能以多种蛋白质形式存在，可能执行不同的功能。本综述致力于描述结构和功能多样性以及 Hp 作为各种病理学生物标志物的潜在用途。这些特征表明 Hp 可能以多种蛋白质形式存在，可能执行不同的功能。本综述致力于描述结构和功能多样性以及 Hp 作为各种病理学生物标志物的潜在用途。这些特征表明 Hp 可能以多种蛋白质形式存在，可能执行不同的功能。本综述致力于描述结构和功能多样性以及 Hp 作为各种病理学生物标志物的潜在用途。