A tale of two citrullines--structural and functional aspects of myelin basic protein deimination in health and disease

• Published in: Neurochemical research 2007-02, Vol.32 (2), p.137-158
• Main Authors: Harauz, George, Musse, Abdiwahab A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Arthritis, Rheumatoid - physiopathology; Citrulline - physiology; Humans; Hydrolases - metabolism; Molecular Sequence Data; Multiple Sclerosis - physiopathology; Myelin Basic Protein - chemistry; Myelin Basic Protein - physiology; Myelin Sheath - chemistry; Myelin Sheath - metabolism; Protein Conformation; Protein Processing, Post-Translational; Protein-Arginine Deiminases
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-006-9108-9

Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.