Abstract
A protein undergoes many types of posttranslation modification. Citrullination is one of these modifications, where an arginine amino acid is converted to a citrulline amino acid. This process depends on catalytic enzymes such as peptidylarginine deiminase enzymes (PADs). This modification leads to a charge shift, which affects the protein structure, protein-protein interactions, and hydrogen bond formation, and it may cause protein denaturation. The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells. A defect in the clearance system either in terms of efficiency or capacity may occur due to massive cell death, which may result in the accumulation and leakage of PAD enzymes and the citrullinated peptide from the necrotized cell which could be recognized by the immune system, where the immunological tolerance will be avoided and the autoimmune disorders will be subsequently triggered. The induction of autoimmune responses, autoantibody production, and cytokines involved in the major autoimmune diseases will be discussed.
Highlights
Most of the known proteins synthesized by ribosomes through the translation of mRNA are modified in a process known as posttranslational modification (PTM)
The specific reason underlying peptidylarginine deiminase enzymes (PADs) dysregulation is not well defined, but there are many factors which may explain abnormal citrullination such as high levels of calcium that may affect PAD target specificity and their activity, unchecked translation of protein arginine deiminases that could cause an increase in citrullination [87], abnormal tumor necrosis factor alpha (TNF-α) signaling that is characteristic of ulcerative colitis (UC) and rheumatoid arthritis (RA), and TNF-α that can induce the translocation of PAD4 [88]
HLA typing was performed to detect the presence of HLA-DRB1 shared epitopes (SE), which is known as a genetic risk factor contributing to RA
Summary
Most of the known proteins synthesized by ribosomes through the translation of mRNA are modified in a process known as posttranslational modification (PTM). PTMs are regulatory processes which have a significant role in the functional diversity, stability, and interactions of proteins with other molecules. These modification processes include physical and chemical changes of a protein or its particular amino acid. The physical modification involves protein folding facilitated by a chaperone protein, while the chemical modification has a different mechanism and different forms. There are different types of covalent modifications of the protein, which occur by the addition of chemical groups such as in phosphorylation, acetylation, hydroxylation, and methylation. The modification of amino acids is another form of PTM, which involves deamidation, eliminylation, and citrullination. The autoimmune responses attributed to citrullinated proteins will be involved. Journal of Immunology Research on the prevalence of citrullination-related diseases in the Saudi population
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