What is citrullination in rheumatoid arthritis?
Citrullination, the post-translational conversion of arginine to citrulline residues by peptidylarginine deiminase enzymes (PADs), is thought to be an essential contributor to the rheumatoid arthritis (RA) disease pathogenesis.
What is the function of citrullination?
Citrullination has an important role in the normal function of the immune system, skin keratinization, the insulation of neurons and the plasticity of the central nervous system including its essential role in gene regulation.
How does citrullination occur?
Histone citrullination occurs by enzymatic conversion of arginine residue to citrulline. This leads to chromatin relaxation and enables activation of transcription.
Is citrullination reversible?
In contrast to many other posttranslational modification (PTM), citrullination appears to be an irreversible process.
Is citrullination a normal process?
Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells.
What causes citrullination of proteins?
, peptidylarginine deiminase (PAD)-containing inflammatory cells infiltrate the site of inflammation. At the onset of death of these cells, the intracellular calcium concentration is raised, thereby causing activation of PAD enzymes and consequently citrullination of proteins.
What is citrullination and why is it important?
Citrullinated proteins are also found in the cellular debris accompanying the destruction of cells in alzheimer disease, and after smoking cigarettes. So citrullination seems to be part of the mechanism that stimulates the immune system in autoimmune disease.
What is deimination or citrullination?
Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline.
What is citrullination of vimentin?
The citrullination of vimentin is thought to be mediated by PAD2 and results in a loss of vimentin’s normal function, leading to filament instability, inability to polymerize in vitro, and the collapse of the vimentin cytoskeleton in cells 4,22.
What is a citrullinated protein?
Proteins that normally contain citrulline residues include myosin basic protein, fillagrin, and several histone proteins, whereas other proteins such as fibrinogen, fibrin, and vimentin can be citrullinated during cell death and tissue inflammation. Citrullinated protein antigens are the dominant targets of the autoimmune response in RA.