Deciphering the Sequence Specificity of Protein Citrullination of Glial Fibrillary Acidic Protein

摘要

Multiple sclerosis (MS), a devastating autoimmune disorder affecting between 58 and 95 of every 100,000 people living in the United States (Noonan, 2010), is characterized by damage to the myelin sheath of nerves (Anziolitti, 2010). It is widely believed that citrullination of specific proteins expressed in nervous tissue, such as glial fibrillary acidic protein (GFAP) and myelin basic protein, lies at the root of this disorder. In previous studies of the specificity of arginine citrullination by peptidyl arginine deiminase 4, it has been noted that sequences that promote citrullination within one protein may prove unfavorable towards citrullination in another (Stensland et al (2009), van Beers et al (2010)). Here we describe efforts to map, and predict, citrullination sites in GFAP.