The Effects of Deimination of Myelin Basic Protein on Structures Formed by Its Interaction with Phosphoinositide- Containing Lipid Monolayers

• Published in: Journal of structural biology Vol. 136; no. 1; pp. 30 - 45
• Main Authors: Ishiyama, Noboru, Bates, Ian R, Hill, Christopher M, Wood, D.Denise, Matharu, Philip, Viner, Nick J, Moscarello, Mario A, Harauz, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2001
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Cattle; Circular Dichroism; citrulline; deimination; electron microscopy; Electrophoresis, Polyacrylamide Gel; ganglioside; His tag; Hydrolases - chemistry; lipid tubules; Lipids - chemistry; Mice; Microscopy, Electron; Molecular Sequence Data; multiple sclerosis; myelin basic protein; Myelin Basic Protein - chemistry; Myelin Basic Protein - metabolism; Myelin Sheath - chemistry; phosphatidylinositol; Phosphatidylinositol Phosphates - metabolism; Phosphatidylinositols - metabolism; phosphoinositide; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Protein-Arginine Deiminases; Recombinant Proteins - metabolism; Sequence Homology, Amino Acid; lipid tubules; phosphatidylinositol; multiple sclerosis; electron microscopy; deimination; myelin basic protein; circular dichroism; citrulline; His tag; ganglioside; phosphoinositide
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1006/jsbi.2001.4421

The recombinant 18.5-kDa charge isoform of murine myelin basic protein (rmMBP) is unmodified posttranslationally and was used to study the effects of deimination, i.e., the conversion of arginyl to citrullinyl residues, on the protein's interactions with itself and with lipids. The unmodified species rmMBP-Cit0 (i.e., containing no citrullinyl residues) interacted with binary monolayers containing acidic (phosphatidylinositol) and nickel-chelating lipids to form paracrystalline arrays with 4.8-nm spacing. A sample of protein was deiminated to an average of 9 citrullinyl residues per molecule of protein, yielding rmMBP-Cit9. Under both low- and high-salt conditions, this species formed better-ordered domains than rmMBP-Cit0, viz., planar crystalline assemblies. Thus, deimination of MBP resulted in a significant alteration of its lipid-organizing and self-interaction properties that might be operative in myelin in vivo, especially in progression of the autoimmune disease multiple sclerosis. Comparisons of amino acid sequences indicated significant similarities of MBP with filaggrin, a protein that is deiminated in another autoimmune disease, rheumatoid arthritis, suggesting that comparable epitopes could be targeted in both pathologies. In contrast, binary lipid monolayers consisting of phosphatidylinositol-4-phosphate (or phosphatidylinositol-4,5-bisphosphate) and a nickel-chelating lipid formed helical tubular vesicular structures, which appeared to be induced and/or stabilized by rmMBP, especially in its deiminated form. Sequence comparisons with other actin- and phosphoinositide-binding proteins (vinculin, ActA, MARCKS) suggested that the carboxyl-terminal segment of MBP could form an amphipathic α helix and was the phosphoinositide binding site.