Taldaev Amir, Rudnev Vladimir, Kulikova Liudmila, Nikolsky Kirill, Efimov Alexander, Malsagova Kristina, Kaysheva Anna
Biobanking Group, Branch of IBMC "Scientific and Education Center", 109028 Moscow, Russia.
Department of Chemistry, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
Proteomes. 2022 Feb 11;10(1):8. doi: 10.3390/proteomes10010008.
Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule.
蛋白质翻译后修饰（PTM）对细胞功能、发育、分化和存活的生物活性调节至关重要。PTM蛋白的失调存在于包括类风湿性关节炎（RA）在内的各种病理状况中。RA是一种主要影响关节的全身性自身免疫性疾病，与该疾病发展相关的蛋白质PTM主要有三种类型，即糖基化、瓜氨酸化和氨甲酰化。糖基化对于细胞表面抗原片段的加工和呈递很重要，并且可以调节免疫球蛋白活性。自身抗原的瓜氨酸化与RA密切相关，患者血清中存在瓜氨酸化蛋白特异性抗体就证明了这一点。氨甲酰化及其失调最近被认为与人类RA的发展有关。在本研究中，我们对过去20年同行评审科学论文中提及的与RA发展相关的翻译后修饰蛋白进行了综述分析。通过检索，形成了一份RA中具有PTM的靶蛋白及其相应氨基酸序列的列表。列出的修饰蛋白的结构特征从蛋白质数据库中提取。然后，针对ProtDB服务中公布的列表中的结构，对完整蛋白质结构以及具有PTM的相应结构进行了分子动力学实验。本研究旨在对完整蛋白质以及可能与RA发展相关的包括翻译后修饰和蛋白质瓜氨酸化的蛋白质进行分子动力学研究。我们在亚分子水平上观察到了基本物理概念对称性的另一种表现形式，表现为蛋白质结构基序性能球外部与整个蛋白质分子中相应部分的自主重复。
