MyelStones: The executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis

Biochemical Journal

Volumn 472, Issue 1, 2015, Pages 17-32

  Vassall, Kenrick A ^a   Bamm, Vladimir V ^a   Harauz, George ^a  

^a UNIVERSITY OF GUELPH   (Canada)

Author keywords

Amphipathic helix; Cis trans prolyl isomerization; Deimination; Fyn SH3; Intrinsically disordered protein (IDP); Molecular recognition fragment (MoRF); Multiple sclerosis (MS); Myelin basic protein (MBP); Phosphorylation; Polyproline II (PPII) conformation

Indexed keywords

INTRINSICALLY DISORDERED PROTEIN; MYELIN; MYELIN BASIC PROTEIN; ISOPROTEIN;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ARTICLE; BETA SHEET; CENTRAL NERVOUS SYSTEM; CONFORMATIONAL TRANSITION; DEMYELINATION; HUMAN; IN VITRO STUDY; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STABILITY; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; THERMODYNAMICS; WHITE MATTER; CHEMICAL STRUCTURE; CHEMISTRY; METABOLISM; MYELIN SHEATH; OLIGODENDROGLIA; PHOSPHORYLATION; PROTEIN SECONDARY STRUCTURE;

HUMANS; INTRINSICALLY DISORDERED PROTEINS; MODELS, MOLECULAR; MULTIPLE SCLEROSIS; MYELIN BASIC PROTEIN; MYELIN SHEATH; OLIGODENDROGLIA; PHOSPHORYLATION; PROTEIN ISOFORMS; PROTEIN STRUCTURE, SECONDARY;

EID: 84945967437     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20150710     Document Type: Article

References (276)

1. Morell, P. (1984) Myelin, Plenum Press, New York
2. Lazzarini, R.A., Griffin, J.W., Lassman, H., Nave, K.-A., Miller, R.H. and Trapp, B.D.(2004) Myelin Biology and Disorders, Elsevier Academic Press, San Diego
3. Funfschilling, U., Supplie, L.M., Mahad, D., Boretius, S., Saab, A.S., Edgar, J., Brinkmann, B.G., Kassmann, C.M., Tzvetanova, I.D., Mobius, W. et al. (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485, 517-521 PubMed
4. Nave, K.A. and Werner, H.B. (2014) Myelination of the nervous system: mechanisms and functions. Annu. Rev. Cell Dev. Biol. 30, 503-533 CrossRef PubMed
5. Bercury, K.K. and Macklin, W.B. (2015) Dynamics and mechanisms of CNS myelination. Dev. Cell 32, 447-458 CrossRef PubMed
6. Miller, D.J., Duka, T., Stimpson, C.D., Schapiro, S.J., Baze, W.B., McArthur, M.J., Fobbs, A.J., Sousa, A.M., Sestan, N., Wildman, D.E. et al. (2012) Prolonged myelination in human neocortical evolution. Proc. Natl. Acad. Sci. U.S.A. 109, 16480-16485 CrossRef PubMed
7. Snaidero, N., Mobius, W., Czopka, T., Hekking, L.H., Mathisen, C., Verkleij, D., Goebbels, S., Edgar, J., Merkler, D., Lyons, D.A. et al. (2014) Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue. Cell 156, 277-290 CrossRef PubMed
8. Tomassy, G.S., Berger, D.R., Chen, H.H., Kasthuri, N., Hayworth, K.J., Vercelli, A., Seung, H.S., Lichtman, J.W. and Arlotta, P. (2014) Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex. Science 344, 319-324 CrossRef PubMed
9. de Hoz, L. and Simons, M. (2015) The emerging functions of oligodendrocytes in regulating neuronal network behaviour. BioEssays 37, 60-69 CrossRef PubMed
10. Fields, R.D. (2005) Myelination: an overlooked mechanism of synaptic plasticity? Neuroscientist 11, 528-531 CrossRef PubMed
11. Wake, H., Lee, P.R. and Fields, R.D. (2011) Control of local protein synthesis and initial events in myelination by action potentials. Science 333, 1647-1651 CrossRef PubMed
12. Zatorre, R.J., Fields, R.D. and Johansen-Berg, H. (2012) Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat. Neurosci. 15, 528-536 CrossRef PubMed
13. Young, K.M., Psachoulia, K., Tripathi, R.B., Dunn, S.J., Cossell, L., Attwell, D., Tohyama, K. and Richardson, W.D. (2013) Oligodendrocyte dynamics in the healthy adult CNS: Evidence for myelin remodeling. Neuron 77, 873-885 CrossRef PubMed
14. Wang, S. and Young, K.M. (2014) White matter plasticity in adulthood. Neuroscience 276, 148-160 CrossRef PubMed
15. Chernoff, G.F. (1981) Shiverer: an autosomal recessive mutant mouse with myelin deficiency. J. Hered. 72, 128 PubMed
16. Moscarello, M.A. (1997) Myelin basic protein, the "executive" molecule of the myelin membrane. In Cell Biology and Pathology of Myelin: Evolving Biological Concepts and Therapeutic Approaches (Juurlink, B.H.J., Devon, R.M., Doucette, J.R., Nazarali, A.J., Schreyer, D.J. and Verge, V.M.K., eds), pp. 13-25, Plenum Press, New York CrossRef
17. Roboz-Einstein, E., Robertson, D.M., DiCaprio, J.M. and Moore, W. (1962) Isolation from bovine spinal cord of a homogeneous protein with encephalitogenic activity. J. Neurochem. 9, 353-361 CrossRef PubMed
18. Carnegie, P.R. and Lumsden, C.E. (1966) Encephalitogenic peptides from spinal cord. Nature 209, 1354-1355 CrossRef PubMed
19. Pribyl, T.M., Campagnoni, C.W., Kampf, K., Kashima, T., Handley, V.W., McMahon, J. and Campagnoni, A.T. (1993) The human myelin basic protein gene is included within a 179-kilobase transcription unit: expression in the immune and central nervous systems. Proc. Natl. Acad. Sci. U.S.A. 90, 10695-10699 CrossRef PubMed
20. Campagnoni, A.T., Pribyl, T.M., Campagnoni, C.W., Kampf, K., Amur-Umarjee, S., Landry, C.F., Handley, V.W., Newman, S.L., Garbay, B. and Kitamura, K. (1993) Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. J. Biol. Chem. 268, 4930-4938 PubMed
21. Fulton, D., Paez, P.M. and Campagnoni, A.T. (2010) The multiple roles of myelin protein genes during the development of the oligodendrocyte. ASN Neuro 2, e00027 CrossRef PubMed
22. Siu, C.R., Balsor, J.L., Jones, D.G. and Murphy, K.M. (2015) Classic and golli myelin basic protein have distinct developmental trajectories in human visual cortex. Front. Neurosci 9, 138 CrossRef PubMed
23. Nawaz, S., Schweitzer, J., Jahn, O. and Werner, H.B. (2013) Molecular evolution of myelin basic protein, an abundant structural myelin component. Glia 61, 1364-1377 CrossRef PubMed
24. Werner, H.B. (2013) Do we have to reconsider the evolutionary emergence of myelin? Front. Cell. Neurosci. 7, 217 CrossRef PubMed
25. Boggs, J.M. (2008) Myelin Basic Protein, Nova Science Publishers, Hauppauge
26. Harauz, G. and Boggs, J.M. (2013) Myelin management by the 18.5-kDa and 21.5-kDa classic myelin basic protein isoforms. J. Neurochem. 125, 334-361 CrossRef PubMed
27. Harauz, G., Ladizhansky, V. and Boggs, J.M. (2009) Structural polymorphism and multifunctionality of myelin basic protein. Biochemistry 48, 8094-8104 CrossRef PubMed
28. Harauz, G. and Libich, D.S. (2009) The classic basic protein of myelin-conserved structural motifs and the dynamic molecular barcode involved in membrane adhesion and protein-protein interactions. Curr. Protein Pept. Sci. 10, 196-215 CrossRef PubMed
29. Harauz, G, Libich, D.S., Polverini, E. and Vassall, K.A. (2013) The classic protein of myelin-conserved structural motifs and the dynamic molecular barcode involved in membrane adhesion, protein-protein interactions, and pathogenesis in multiple sclerosis. In Advances in Protein and Peptide Science (Dunn, B.M., ed.), pp. 1-53, Bentham Science Publishers, Oak Park
30. Bakhti, M., Aggarwal, S. and Simons, M. (2014) Myelin architecture: zippering membranes tightly together. Cell. Mol. Life Sci. 71, 1265-1277 CrossRef PubMed
31. Muller, C., Bauer, N.M., Schafer, I. and White, R. (2013) Making myelin basic protein-from mRNA transport to localized translation. Front. Cell Neurosci. 7, 169 PubMed
32. Smith, G.S.T., Seymour, L.V., Boggs, J.M. and Harauz, G. (2012) The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal. Biochem. Biophys. Res. Commun. 422, 670-675 CrossRef PubMed
33. Smith, G.S.T., Samborska, B., Hawley, S.P., Klaiman, J.M., Gillis, T.E., Jones, N., Boggs, J.M. and Harauz, G. (2013) Nucleus-localized 21.5-kDa myelin basic protein promotes oligodendrocyte proliferation and enhances neurite outgrowth in coculture, unlike the plasma membrane-associated 18.5-kDa isoform. J. Neurosci. Res. 91, 349-362 CrossRef PubMed
34. Ozgen, H., Kahya, N., de Jonge, J.C., Smith, G.S., Harauz, G., Hoekstra, D. and Baron, W. (2014) Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms. Biochim. Biophys. Acta 1843, 517-530 CrossRef PubMed
35. Martenson, R.E. (1980) Myelin basic protein: what does it do? In Biochemistry of Brain (Kumar, S., ed.), pp. 49-79, Pergamon, Oxford CrossRef
36. Trapp, B.D. and Kidd, G.J. (2004) Structure of the myelinated axon. In Myelin Biology and Disorders (Lazzarini, R.A., Griffin, J.W., Lassman, H., Nave, K.-A., Miller, R.H. and Trapp, B.D., eds), pp. 3-27, Elsevier Academic Press, San Diego
37. Sedzik, J., Blaurock, A.E. and Höchli, M. (1984) Lipid/myelin basic protein multilayers. A model for the cytoplasmic space in central nervous system myelin. J. Mol. Biol. 174, 385-409 CrossRef PubMed
38. Riccio, P., Fasano, A., Borenshtein, N., Bleve-Zacheo, T. and Kirschner, D.A. (2000) Multilamellar packing of myelin modeled by lipid-bound MBP. J. Neurosci. Res. 59, 513-521 CrossRef PubMed
39. Haas, H., Steitz, R., Fasano, A., Liuzzi, G.M., Polverini, E., Cavatorta, P. and Riccio, P. (2007) Laminar order within Langmuir-Blodgett multilayers from phospholipid and myelin basic protein: a neutron reflectivity study. Langmuir 23, 8491-8496 CrossRef PubMed
40. Kattnig, D.R., Bund, T., Boggs, J.M., Harauz, G. and Hinderberger, D. (2012) Lateral self-assembly of 18.5-kDa myelin basic protein (MBP) charge component-C1 on membranes. Biochim. Biophys. Acta 1818, 2636-2647 CrossRef PubMed
41. Bakhti, M., Snaidero, N., Schneider, D., Aggarwal, S., Mobius, W., Janshoff, A., Eckhardt, M., Nave, K.A. and Simons, M. (2013) Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system. Proc. Natl. Acad. Sci. U.S.A. 110, 3143-3148 CrossRef PubMed
42. Aggarwal, S., Snaidero, N., Pahler, G., Frey, S., Sanchez, P., Zweckstetter, M., Janshoff, A., Schneider, A., Weil, M.T., Schaap, I.A. et al. (2013) Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork. PLoS Biol. 11, e1001577 CrossRef PubMed
43. Bamm, V.V., Ahmed, M.A. and Harauz, G. (2010) Interaction of myelin basic protein with actin in the presence of dodecylphosphocholine micelles. Biochemistry 49, 6903-6915 CrossRef PubMed
44. Boggs, J.M., Homchaudhuri, L., Ranagaraj, G., Liu, Y., Smith, G.S. and Harauz, G. (2014) Interaction of myelin basic protein with cytoskeletal and signaling proteins in cultured primary oligodendrocytes and N19 oligodendroglial cells. BMC Res. Notes 7, 387-14 CrossRef PubMed
45. Smith, G.S.T., De Avila, M., Paez, P.M., Spreuer, V., Wills, M.K.B., Jones, N., Boggs, J.M. and Harauz, G. (2012) Proline substitutions and threonine pseudophosphorylation of the SH3 ligand of 18.5-kDa myelin basic protein decrease its affinity for the Fyn-SH3 domain and alter process development and protein localization in oligodendrocytes. J. Neurosci. Res. 90, 28-47 CrossRef PubMed
46. Ahmed, M.A.M., De Avila, M., Polverini, E., Bessonov, K., Bamm, V.V. and Harauz, G. (2012) Solution NMR structure and molecular dynamics simulations of murine 18.5-kDa myelin basic protein segment (S72-S107) in association with dodecylphosphocholine micelles. Biochemistry 51, 7475-7487 CrossRef PubMed
47. De Avila, M., Vassall, K.A., Smith, G.S.T., Bamm, V.V. and Harauz, G. (2014) The proline-rich region of 18.5-kDa myelin basic protein binds to the SH3-domain of Fyn tyrosine kinase with the aid of an upstream segment to form a dynamic complex in vitro. Biosci. Rep. 34, e00157 CrossRef PubMed
48. Smith, G.S.T., Homchaudhuri, L., Boggs, J.M. and Harauz, G. (2012) Classic 18.5-and 21.5-kDa myelin basic protein isoforms associate with cytoskeletal and SH3-domain proteins in the immortalized N19-oligodendroglial cell line stimulated by phorbol ester and IGF-1. Neurochem. Res. 37, 1277-1295 CrossRef PubMed
49. D'Souza, C.A., Wood, D.D., She, Y.M. and Moscarello, M.A. (2005) Autocatalytic cleavage of myelin basic protein: an alternative to molecular mimicry. Biochemistry 44, 12905-12913 CrossRef PubMed
50. Lutz, D., Loers, G., Kleene, R., Oezen, I., Kataria, H., Katagihallimath, N., Braren, I., Harauz, G. and Schachner, M. (2014) Myelin basic protein cleaves cell adhesion molecule L1 and promotes neuritogenesis and cell survival. J. Biol. Chem. 289, 13503-13518 CrossRef PubMed
51. Baran, C., Smith, G.S.T., Bamm, V.V., Harauz, G. and Lee, J.S. (2010) Divalent cations induce a compaction of intrinsically disordered myelin basic protein. Biochem. Biophys. Res. Commun. 391, 224-229 CrossRef PubMed
52. Smith, G.S.T., Chen, L., Bamm, V.V., Dutcher, J.R. and Harauz, G. (2010) The interaction of zinc with membrane-associated 18.5 kDa myelin basic protein: an attenuated total reflectance-Fourier transform infrared spectroscopic study. Amino Acids 39, 739-750 CrossRef PubMed
53. Bund, T., Boggs, J.M., Harauz, G., Hellmann, N. and Hinderberger, D. (2010) Copper uptake induces self-assembly of 18.5-kDa myelin basic protein (MBP). Biophys. J. 99, 3020-3028 CrossRef PubMed
54. Musse, A.A., Gao, W., Homchaudhuri, L., Boggs, J.M. and Harauz, G. (2008) Myelin basic protein as a "PI(4,5)P2-modulin": a new biological function for a major central nervous system protein. Biochemistry 47, 10372-10382 CrossRef PubMed
55. Musse, A.A., Gao, W., Rangaraj, G., Boggs, J.M. and Harauz, G. (2009) Myelin basic protein co-distributes with other PI(4,5)P2-sequestering proteins in Triton X-100 detergent-resistant membrane microdomains. Neurosci. Lett. 450, 32-36 CrossRef PubMed
56. Nawaz, S., Kippert, A., Saab, A.S., Werner, H.B., Lang, T., Nave, K.A. and Simons, M. (2009) Phosphatidylinositol 4,5-bisphosphate-dependent interaction of myelin basic protein with the plasma membrane in oligodendroglial cells and its rapid perturbation by elevated calcium. J. Neurosci. 29, 4794-4807 CrossRef PubMed
57. Zuchero, J.B., Fu, M.M., Sloan, S.A., Ibrahim, A., Olson, A., Zaremba, A., Dugas, J.C., Wienbar, S., Caprariello, A.V., Kantor, C. et al. (2015) CNS myelin wrapping is driven by actin disassembly. Dev. Cell 34, 152-167 CrossRef PubMed
58. Boggs, J.M., Rangaraj, G., Gao, W. and Heng, Y.M. (2006) Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro. Biochemistry 45, 391-401 CrossRef PubMed
59. Homchaudhuri, L., Polverini, E., Gao, W., Harauz, G. and Boggs, J.M. (2009) Influence of membrane surface charge and post-translational modifications to myelin basic protein on its ability to tether the Fyn-SH3 domain to a membrane in vitro. Biochemistry 48, 2385-2393 CrossRef PubMed
60. Boggs, J.M., Rangaraj, G. and Dicko, A. (2012) Effect of phosphorylation of phosphatidylinositol on myelin basic protein-mediated binding of actin filaments to lipid bilayers in vitro. Biochim. Biophys. Acta 1818, 2217-2227 CrossRef PubMed
61. Hill, C.M.D., Libich, D.S. and Harauz, G. (2005) Assembly of tubulin by classic myelin basic protein isoforms and regulation by post-translational modification. Biochemistry 44, 16672-16683 CrossRef PubMed
62. Hill, C.M.D. and Harauz, G. (2005) Charge effects modulate actin assembly by classic myelin basic protein isoforms. Biochem. Biophys. Res. Commun. 329, 362-369 CrossRef PubMed
63. Libich, D.S. and Harauz, G. (2008) Backbone dynamics of the 18.5-kDa isoform of myelin basic protein reveals transient alpha-helices and a calmodulin-binding site. Biophys. J. 94, 4847-4866 CrossRef PubMed
64. Homchaudhuri, L., De Avila, M., Nilsson, S.B., Bessonov, K., Smith, G.S.T., Bamm, V.V., Musse, A.A., Harauz, G. and Boggs, J.M. (2010) Secondary structure and solvent accessibility of a calmodulin-binding C-terminal segment of membrane-associated myelin basic protein. Biochemistry 49, 8955-8966 CrossRef PubMed
65. Bamm, V.V., De Avila, M., Smith, G.S.T., Ahmed, M.A. and Harauz, G. (2011) Structured functional domains of myelin basic protein: cross talk between actin polymerization and Ca(2+)-dependent calmodulin interaction. Biophys. J. 101, 1248-1256 CrossRef PubMed
66. Nawaz, S., Sanchez, P., Schmitt, S., Snaidero, N., Mitkovski, M., Velte, C., Bruckner, B.R., Alexopoulos, I., Czopka, T., Jung, S.Y. et al. (2015) Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system. Dev. Cell 34, 139-151 CrossRef PubMed
67. Moscarello, M.A., Gagnon, J., Wood, D.D., Anthony, J. and Epand, R. (1973) Conformational flexibility of a myelin protein. Biochemistry 12, 3402-3406 CrossRef PubMed
68. Krigbaum, W.R. and Hsu, T.S. (1975) Molecular conformation of bovine A1 basic protein, a coiling macromolecule in aqueous solution. Biochemistry 14, 2542-2546 CrossRef PubMed
69. Epand, R.M., Moscarello, M.A., Zierenberg, B. and Vail, W.J. (1974) The folded conformation of the encephalitogenic protein of the human brain. Biochemistry 13, 1264-1267 CrossRef PubMed
70. Feinstein, M.B. and Felsenfeld, H. (1975) Reactions of fluorescent probes with normal and chemically modified myelin basic protein and proteolipid. Comparisons with myelin. Biochemistry 14, 3049-3056
71. Smith, R. (1977) Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation. Biochim. Biophys. Acta 470, 170-184 CrossRef PubMed
72. Chapman, B.E., Littlemore, L.T. and Moore, W.J. (1978) Conformation of myelin basic protein and its role in myelin formation. Adv. Exp. Med. Biol. 100, 207-220 CrossRef PubMed
73. Martenson, R.E. (1978) The use of gel filtration to follow conformational changes in proteins. Conformational flexibility of bovine myelin basic protein. J. Biol. Chem. 253, 8887-8893 PubMed
74. Randall, C.S. and Zand, R. (1985) Spectroscopic assessment of secondary and tertiary structure in myelin basic protein. Biochemistry 24, 1998-2004 CrossRef PubMed
75. Caamaño, C.A. and Zand, R. (1989) Resolution and solution behavior of crosslinked myelin basic protein. Biochem. Int. 18, 1245-1251 PubMed
76. Gow, A. and Smith, R. (1989) The thermodynamically stable state of myelin basic protein in aqueous solution is a flexible coil. Biochem. J. 257, 535-540 CrossRef PubMed
77. Moscarello, M.A. (1990) Myelin basic protein: a dynamically changing structure. Prog. Clin. Biol. Res. 336, 25-48 PubMed
78. Nowak, M.W. and Berman, H.A. (1991) Fluorescence studies on the interactions of myelin basic protein in electrolyte solutions. Biochemistry 30, 7642-7651 CrossRef PubMed
79. Stoner, G.L. (1984) Predicted folding of beta-structure in myelin basic protein. J. Neurochem. 43, 433-447 CrossRef PubMed
80. Martenson, R.E. (1986) Possible hydrophobic region in myelin basic protein consisting of an orthogonally packed beta-sheet. J. Neurochem. 46, 1612-1622 CrossRef PubMed
81. Stoner, G.L. (1990) Conservation throughout vertebrate evolution of the predicted beta-strands in myelin basic protein. J. Neurochem. 55, 1404-1411 CrossRef PubMed
82. Keniry, M.A. and Smith, R. (1981) Dependence on lipid structure of the coil-to-helix transition of bovine myelin basic protein. Biochim. Biophys. Acta 668, 107-118 CrossRef PubMed
83. Mendz, G.L., Moore, W.J., Brown, L.R. and Martenson, R.E. (1984) Interaction of myelin basic protein with micelles of dodecylphosphocholine. Biochemistry 23, 6041-6046 CrossRef PubMed
84. Mendz, G.L., Brown, L.R. and Martenson, R.E. (1990) Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles. Biochemistry 29, 2304-2311 CrossRef PubMed
85. Polverini, E., Fasano, A., Zito, F., Riccio, P. and Cavatorta, P. (1999) Conformation of bovine myelin basic protein purified with bound lipids. Eur. Biophys. J. 28, 351-355 CrossRef PubMed
86. Smith, R. (1992) The basic protein of CNS myelin: its structure and ligand binding. J. Neurochem. 59, 1589-1608 CrossRef PubMed
87. Harauz, G., Ishiyama, N., Hill, C.M.D., Bates, I.R., Libich, D.S. and Farès, C. (2004) Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis. Micron 35, 503-542 CrossRef PubMed
88. Beniac, D.R., Luckevich, M.D., Czarnota, G.J., Tompkins, T.A., Ridsdale, R.A., Ottensmeyer, F.P., Moscarello, M.A. and Harauz, G. (1997) Three-dimensional structure of myelin basic protein. I. Reconstruction via angular reconstitution of randomly oriented single particles. J. Biol. Chem. 272, 4261-4268 CrossRef PubMed
89. Beniac, D.R., Wood, D.D., Palaniyar, N., Ottensmeyer, F.P., Moscarello, M.A. and Harauz, G. (2000) Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination. J. Struct. Biol. 129, 80-95 CrossRef PubMed
90. Ridsdale, R.A., Beniac, D.R., Tompkins, T.A., Moscarello, M.A. and Harauz, G. (1997) Three-dimensional structure of myelin basic protein. II. Molecular modeling and considerations of predicted structures in multiple sclerosis. J. Biol. Chem. 272, 4269-4275 CrossRef PubMed
91. Bates, I.R. and Harauz, G. (2003) Molecular dynamics exposes a-helices in myelin basic protein. J. Mol. Model. 9, 290-297 CrossRef PubMed
92. Haas, H., Oliveira, C.L.P., Torriani, I.L., Polverini, E., Fasano, A., Carlone, G., Cavatorta, P. and Riccio, P. (2004) Small angle X-ray scattering from lipid-bound myelin basic protein in solution. Biophys. J. 86, 455-460 CrossRef PubMed
93. Stadler, A.M., Stingaciu, L., Radulescu, A., Holderer, O., Monkenbusch, M., Biehl, R. and Richter, D. (2014) Internal nanosecond dynamics in the intrinsically disordered myelin basic protein. J. Am. Chem. Soc. 136, 6987-6994 CrossRef PubMed
94. Lee, D.W., Banquy, X., Kristiansen, K., Min, Y., Ramachandran, A., Boggs, J.M. and Israelachvili, J.N. (2015) Adsorption mechanism of myelin basic protein on model substrates and its bridging interaction between the two surfaces. Langmuir 31, 3159-3166 CrossRef PubMed
95. Uversky, V.N., Gillespie, J.R. and Fink, A.L. (2000) Why are "natively unfolded" proteins unstructured under physiologic conditions? Proteins 41, 415-427 CrossRef PubMed
96. Hill, C.M.D., Bates, I.R., White, G.F., Hallett, F.R. and Harauz, G. (2002) Effects of the osmolyte trimethylamine-N-oxide on conformation, self-association, and two-dimensional crystallization of myelin basic protein. J. Struct. Biol. 139, 13-26 CrossRef PubMed
97. Wright, P.E. and Dyson, H.J. (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321-331 CrossRef PubMed
98. Tompa, P. (2012) Intrinsically disordered proteins: a 10-year recap. Trends Biochem. Sci. 37, 509-516 CrossRef PubMed
99. Tompa, P. and Fersht, A. (2015) Structure and Function of Intrinsically Disordered Proteins, Chapman and Hall/CRC Press, London
100. Sedzik, J. and Kirschner, D.A. (1992) Is myelin basic protein crystallizable? Neurochem. Res. 17, 157-166 CrossRef PubMed
101. Xue, B., Dunbrack, R.L., Williams, R.W., Dunker, A.K. and Uversky, V.N. (2010) PONDR-FIT: a meta-predictor of intrinsically disordered amino acids. Biochim. Biophys. Acta 1804, 996-1010 CrossRef PubMed
102. Mittag, T. and Forman-Kay, J.D. (2007) Atomic-level characterization of disordered protein ensembles. Curr. Opin. Struct. Biol. 17, 3-14 CrossRef PubMed
103. Marsh, J.A. and Forman-Kay, J.D. (2009) Structure and disorder in an unfolded state under nondenaturing conditions from ensemble models consistent with a large number of experimental restraints. J. Mol. Biol. 391, 359-374 CrossRef PubMed
104. Tompa, P. (2005) The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett. 579, 3346-3354 CrossRef PubMed
105. Cumberworth, A., Lamour, G., Babu, M.M. and Gsponer, J. (2013) Promiscuity as a functional trait: intrinsically disordered regions as central players of interactomes. Biochem. J. 454, 361-369 CrossRef PubMed
106. Tompa, P., Szasz, C. and Buday, L. (2005) Structural disorder throws new light on moonlighting. Trends Biochem. Sci. 30, 484-489 CrossRef PubMed
107. Fuxreiter, M. and Tompa, P. (2012) Fuzzy complexes: a more stochastic view of protein function. Adv. Exp. Med. Biol. 725, 1-14 CrossRef PubMed
108. Tompa, P. and Fuxreiter, M. (2008) Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem. Sci. 33, 2-8 CrossRef PubMed
109. Uversky, V.N. (2009) Intrinsic disorder in proteins associated with neurodegenerative diseases. Front. Biosci. (Landmark Ed.) 14, 5188-5238 CrossRef PubMed
110. Uversky, V.N., Dave, V., Iakoucheva, L.M., Malaney, P., Metallo, S.J., Pathak, R.R. and Joerger, A.C. (2014) Pathological unfoldomics of uncontrolled chaos: Intrinsically disordered proteins and human diseases. Chem. Rev. 114, 6844-6879 CrossRef PubMed
111. Fuxreiter, M., Toth-Petroczy, A., Kraut, D.A., Matouschek, A.T., Lim, R.Y., Xue, B., Kurgan, L. and Uversky, V.N. (2014) Disordered proteinaceous machines. Chem. Rev. 114, 6806-6843 CrossRef PubMed
112. Wright, P.E. and Dyson, H.J. (2015) Intrinsically disordered proteins in cellular signalling and regulation. Nat. Rev. Mol. Cell Biol. 16, 18-29 CrossRef PubMed
113. Bates, I.R., Feix, J.B., Boggs, J.M. and Harauz, G. (2004) An immunodominant epitope of myelin basic protein is an amphipathic alpha-helix. J. Biol. Chem. 279, 5757-5764 CrossRef PubMed
114. Ishiyama, N., Bates, I.R., Hill, C.M.D., Wood, D.D., Matharu, P., Viner, N.J., Moscarello, M.A. and Harauz, G. (2001) The effects of deimination of myelin basic protein on structures formed by its interaction with phosphoinositide-containing lipid monolayers. J. Struct. Biol. 136, 30-45 CrossRef PubMed
115. Libich, D.S. and Harauz, G. (2008) Solution NMR and CD spectroscopy of an intrinsically disordered, peripheral membrane protein: evaluation of aqueous and membrane-mimetic solvent conditions for studying the conformational adaptability of the 18.5 kDa isoform of myelin basic protein (MBP). Eur. Biophys. J. 37, 1015-1029 CrossRef PubMed
116. Buck, M. (1998) Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins. Q. Rev. Biophys. 31, 297-355 CrossRef PubMed
117. Roccatano, D., Colombo, G., Fioroni, M. and Mark, A.E. (2002) Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study. Proc. Natl. Acad. Sci. U.S.A. 99, 12179-12184 CrossRef PubMed
118. Povey, J.F., Smales, C.M., Hassard, S.J. and Howard, M.J. (2007) Comparison of the effects of 2,2,2-trifluoroethanol on peptide and protein structure and function. J. Struct. Biol. 157, 329-338 CrossRef PubMed
119. Vassall, K.A., Bessonov, K., De Avila, M., Polverini, E. and Harauz, G. (2013) The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein. PLoS One 8, e68175 CrossRef PubMed
120. Vassall, K.A., Jenkins, A.D., Bamm, V.V. and Harauz, G. (2015) Thermodynamic analysis of the disorder-to-alpha-helical transition of 18.5-kDa myelin basic protein reveals an equilibrium intermediate representing the most compact conformation. J. Mol. Biol. 427, 1977-1992 CrossRef PubMed
121. Oldfield, C.J., Cheng, Y., Cortese, M.S., Romero, P., Uversky, V.N. and Dunker, A.K. (2005) Coupled folding and binding with alpha-helix-forming molecular recognition elements. Biochemistry 44, 12454-12470 CrossRef PubMed
122. Musse, A.A., Boggs, J.M. and Harauz, G. (2006) Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope. Proc. Natl. Acad. Sci. U.S.A. 103, 4422-4427 CrossRef PubMed
123. Ahmed, M.A.M., Bamm, V.V., Harauz, G. and Ladizhansky, V. (2010) Solid-state NMR spectroscopy of membrane-associated myelin basic protein-conformation and dynamics of an immunodominant epitope. Biophys. J. 99, 1247-1255 CrossRef PubMed
124. Muruganandam, G., Burck, J., Ulrich, A.S., Kursula, I. and Kursula, P. (2013) Lipid membrane association of myelin proteins and peptide segments studied by oriented and synchrotron radiation circular dichroism spectroscopy. J. Phys. Chem. B 117, 14983-14993 PubMed
125. Zhong, L., Bamm, V.V., Ahmed, M.A., Harauz, G. and Ladizhansky, V. (2007) Solid-state NMR spectroscopy of 18.5 kDa myelin basic protein reconstituted with lipid vesicles: spectroscopic characterisation and spectral assignments of solvent-exposed protein fragments. Biochim. Biophys. Acta 1768, 3193-3205 CrossRef PubMed
126. Majava, V., Petoukhov, M.V., Hayashi, N., Pirila, P., Svergun, D.I. and Kursula, P. (2008) Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure. BMC Struct. Biol. 8, 10 CrossRef PubMed
127. Wang, C., Neugebauer, U., Burck, J., Myllykoski, M., Baumgartel, P., Popp, J. and Kursula, P. (2011) Charge isomers of myelin basic protein: structure and interactions with membranes, nucleotide analogues, and calmodulin. PLoS One 6, e19915 CrossRef PubMed
128. Nagulapalli, M., Parigi, G., Yuan, J., Gsponer, J., Deraos, G., Bamm, V.V., Harauz, G., Matsoukas, J., de Planque, M.R., Gerothanassis, I.P. et al. (2012) Recognition pliability is coupled to structural heterogeneity: a calmodulin intrinsically disordered binding region complex. Structure 20, 522-533 CrossRef PubMed
129. Zienowicz, A., Bamm, V.V., Vassall, K.A. and Harauz, G. (2015) Myelin basic protein is a glial microtubule-associated protein-characterization of binding domains, kinetics of polymerization, and regulation by phosphorylation and a lipidic environment. Biochem. Biophys. Res. Commun. 461, 136-141 CrossRef PubMed
130. Boggs, J.M., Rangaraj, G., Heng, Y.M., Liu, Y. and Harauz, G. (2011) Myelin basic protein binds microtubules to a membrane surface and to actin filaments in vitro: effect of phosphorylation and deimination. Biochim. Biophys. Acta 1808, 761-773 CrossRef PubMed
131. Polverini, E., Coll, E.P., Tieleman, D.P. and Harauz, G. (2011) Conformational choreography of a molecular switch region in myelin basic protein-molecular dynamics shows induced folding and secondary structure type conversion upon threonyl phosphorylation in both aqueous and membrane-associated environments. Biochim. Biophys. Acta 1808, 674-683 CrossRef PubMed
132. Blair, L.J., Baker, J.D., Sabbagh, J.J. and Dickey, C.A. (2015) The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer's disease. J. Neurochem. 133, 1-13 CrossRef PubMed
133. Polverini, E., Rangaraj, G., Libich, D.S., Boggs, J.M. and Harauz, G. (2008) Binding of the proline-rich segment of myelin basic protein to SH3-domains-spectroscopic, microarray, and modelling studies of ligand conformation and effects of post-translational modifications. Biochemistry 47, 267-282 CrossRef PubMed
134. Bessonov, K., Bamm, V.V. and Harauz, G. (2010) Misincorporation of the proline homologue Aze (azetidine-2-carboxylic acid) into recombinant myelin basic protein. Phytochemistry 71, 502-507 CrossRef PubMed
135. Rath, A., Davidson, A.R. and Deber, C.M. (2005) The structure of "unstructured" regions in peptides and proteins: role of the polyproline II helix in protein folding and recognition. Biopolymers 80, 179-185 CrossRef PubMed
136. Elam, W.A., Schrank, T.P., Campagnolo, A.J. and Hilser, V.J. (2013) Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites. Protein Sci. 22, 405-417 CrossRef PubMed
137. Umemori, H., Sato, S., Yagi, T., Aizawa, S. and Yamamoto, T. (1994) Initial events of myelination involve Fyn tyrosine kinase signalling. Nature 367, 572-576 CrossRef PubMed
138. Krämer-Albers, E.M. and White, R. (2011) From axon-glial signalling to myelination: the integrating role of oligodendroglial Fyn kinase. Cell. Mol. Life Sci. 68, 2003-2012 CrossRef PubMed
139. Umemori, H., Kadowaki, Y., Hirosawa, K., Yoshida, Y., Hironaka, K., Okano, H. and Yamamoto, T. (1999) Stimulation of myelin basic protein gene transcription by Fyn tyrosine kinase for myelination. J. Neurosci. 19, 1393-1397 PubMed
140. White, R., Gonsior, C., Kramer-Albers, E.M., Stohr, N., Huttelmaier, S. and Trotter, J. (2008) Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2-dependent RNA granules. J. Cell Biol. 181, 579-586 CrossRef PubMed
141. Libich, D.S., Ahmed, M.A.M., Zhong, L., Bamm, V.V., Ladizhansky, V. and Harauz, G. (2010) Fuzzy complexes of myelin basic protein: NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system. Biochem. Cell Biol. 88, 143-155 CrossRef PubMed
142. Papoian, G.A. (2008) Proteins with weakly funneled energy landscapes challenge the classical structure-function paradigm. Proc. Natl. Acad. Sci. U.S.A. 105, 14237-14238 CrossRef PubMed
143. Oldfield, C.J. and Dunker, A.K. (2014) Intrinsically disordered proteins and intrinsically disordered protein regions. Annu. Rev. Biochem. 83, 553-584 CrossRef PubMed
144. Bates, I.R., Boggs, J.M., Feix, J.B. and Harauz, G. (2003) Membrane-anchoring and charge effects in the interaction of myelin basic protein with lipid bilayers studied by site-directed spin labeling. J. Biol. Chem. 278, 29041-29047 CrossRef PubMed
145. Ishiyama, N., Hill, C.M.D., Bates, I.R. and Harauz, G. (2002) The formation of helical tubular vesicles by binary monolayers containing a nickel-chelating lipid and phosphoinositides in the presence of basic polypeptides. Chem. Phys. Lipids 114, 103-111 CrossRef PubMed
146. Bates, I.R., Libich, D.S., Wood, D.D., Moscarello, M.A. and Harauz, G. (2002) An Arg/Lys-Gln mutant of recombinant murine myelin basic protein as a mimic of the deiminated form implicated in multiple sclerosis. Protein Expr. Purif. 25, 330-341 CrossRef PubMed
147. Beniac, D.R., Wood, D.D., Palaniyar, N., Ottensmeyer, F.P., Moscarello, M.A. and Harauz, G. (1999) Marburg's variant of multiple sclerosis correlates with a less compact structure of myelin basic protein. Mol. Cell Biol. Res. Commun. 1, 48-51 CrossRef PubMed
148. Pritzker, L.B., Joshi, S., Gowan, J.J., Harauz, G. and Moscarello, M.A. (2000) Deimination of myelin basic protein. 1. Effect of deimination of arginyl residues of myelin basic protein on its structure and susceptibility to digestion by cathepsin D. Biochemistry 39, 5374-5381 CrossRef PubMed
149. D'Souza, C.A. and Moscarello, M.A. (2006) Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope. Neurochem. Res. 31, 1045-1054 CrossRef PubMed
150. Marsh, J.A. and Forman-Kay, J.D. (2010) Sequence determinants of compaction in intrinsically disordered proteins. Biophys. J. 98, 2383-2390 CrossRef PubMed
151. Das, R.K., Mittal, A. and Pappu, R.V. (2013) How is functional specificity achieved through disordered regions of proteins? BioEssays 35, 17-22 CrossRef PubMed
152. Adhikari, J., West, G.M. and Fitzgerald, M.C. (2015) Global analysis of protein folding thermodynamics for disease state characterization. J. Proteome Res. 14, 2287-2297 CrossRef PubMed
153. Earl, C., Chantry, A., Mohammad, N. and Glynn, P. (1988) Zinc ions stabilise the association of basic protein with brain myelin membranes. J. Neurochem. 51, 718-724 CrossRef PubMed
154. Tsang, D., Tsang, Y.S., Ho, W.K. and Wong, R.N. (1997) Myelin basic protein is a zinc-binding protein in brain: possible role in myelin compaction. Neurochem. Res. 22, 811-819 CrossRef PubMed
155. Heller, G.T., Sormanni, P. and Vendruscolo, M. (2015) Targeting disordered proteins with small molecules using entropy. Trends Biochem. Sci. 40, 491-496 CrossRef PubMed
156. Boggs, J.M., Moscarello, M.A. and Papahadjopoulos, D. (1982) Structural organization of myelin: role of lipid-protein interactions determined in model systems. In Lipid-Protein Interactions (Jost, P.C. and Griffith, O.H., eds), pp. 1-51, Wiley-Interscience, New York
157. Boggs, J.M., Wood, D.D. and Moscarello, M.A. (1981) Hydrophobic and electrostatic interactions of myelin basic proteins with lipid. Participation of N-terminal and C-terminal portions. Biochemistry 20, 1065-1073 CrossRef PubMed
158. Jo, E. and Boggs, J.M. (1995) Aggregation of acidic lipid vesicles by myelin basic protein: dependence on potassium concentration. Biochemistry 34, 13705-13716 CrossRef PubMed
159. Stollery, J.G., Boggs, J.M. and Moscarello, M.A. (1980) Variable interaction of spin-labeled human myelin basic protein with different acidic lipids. Biochemistry 19, 1219-1226 CrossRef PubMed
160. Hu, Y., Doudevski, I., Wood, D., Moscarello, M., Husted, C., Genain, C., Zasadzinski, J.A. and Israelachvili, J. (2004) Synergistic interactions of lipids and myelin basic protein. Proc. Natl. Acad. Sci. U.S.A. 101, 13466-13471 CrossRef PubMed
161. Min, Y., Kristiansen, K., Boggs, J.M., Husted, C., Zasadzinski, J.A. and Israelachvili, J. (2009) Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein. Proc. Natl. Acad. Sci. U.S.A. 106, 3154-3159 CrossRef PubMed
162. Wood, D.D. and Moscarello, M.A. (1989) The isolation, characterization, and lipid-aggregating properties of a citrulline containing myelin basic protein. J. Biol. Chem. 264, 5121-5127 PubMed
163. Boggs, J.M., Yip, P.M., Rangaraj, G. and Jo, E. (1997) Effect of posttranslational modifications to myelin basic protein on its ability to aggregate acidic lipid vesicles. Biochemistry 36, 5065-5071 CrossRef PubMed
164. Boggs, J.M., Rangaraj, G., Koshy, K.M., Ackerley, C., Wood, D.D. and Moscarello, M.A. (1999) Highly deiminated isoform of myelin basic protein from multiple sclerosis brain causes fragmentation of lipid vesicles. J. Neurosci. Res. 57, 529-535 CrossRef PubMed
165. Boggs, J.M., Moscarello, M.A. and Papahadjopoulos, D. (1977) Phase separation of acidic and neutral phospholipids induced by human myelin basic protein. Biochemistry 16, 5420-5426 CrossRef PubMed
166. Boggs, J.M. and Moscarello, M.A. (1978) Effect of basic protein from human central nervous system myelin on lipid bilayer structure. J. Membr. Biol. 39, 75-96 CrossRef PubMed
167. Min, Y., Alig, T.F., Lee, D.W., Boggs, J.M., Israelachvili, J.N. and Zasadzinski, J.A. (2011) Critical and off-critical miscibility transitions in model extracellular and cytoplasmic myelin lipid monolayers. Biophys. J. 100, 1490-1498 CrossRef PubMed
168. Napolitano, L., Lebaron, F. and Scaletti, J. (1967) Preservation of myelin lamellar structure in the absence of lipid. A correlated chemical and morphological study. J. Cell Biol. 34, 817-826 CrossRef PubMed
169. Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H.J. and Mandelkow, E. (2006) Global hairpin folding of tau in solution. Biochemistry 45, 2283-2293 CrossRef PubMed
170. von Bergen, M., Barghorn, S., Jeganathan, S., Mandelkow, E.M. and Mandelkow, E. (2006) Spectroscopic approaches to the conformation of tau protein in solution and in paired helical filaments. Neurodegener. Dis. 3, 197-206 CrossRef PubMed
171. Golds, E.E. and Braun, P.E. (1978) Protein associations and basic protein conformation in the myelin membrane. The use of difluorodinitrobenzene as a cross-linking reagent. J. Biol. Chem. 253, 8162-8170 PubMed
172. Smith, R. (1985) The encephalitogenic protein of myelin forms hexamers in which the polypeptides have a pleated-sheet structure. FEBS Lett. 183, 331-334 CrossRef PubMed
173. Bates, I.R., Matharu, P., Ishiyama, N., Rochon, D., Wood, D.D., Polverini, E., Moscarello, M.A., Viner, N.J. and Harauz, G. (2000) Characterization of a recombinant murine 18.5-kDa myelin basic protein. Protein Expr. Purif. 20, 285-299 CrossRef PubMed
174. Hill, C.M.D., Haines, J.D., Antler, C.E., Bates, I.R., Libich, D.S. and Harauz, G. (2003) Terminal deletion mutants of myelin basic protein: new insights into self-association and phospholipid interactions. Micron 34, 25-37 CrossRef PubMed
175. Dyer, C.A. and Benjamins, J.A. (1989) Organization of oligodendroglial membrane sheets. I: association of myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase with cytoskeleton. J. Neurosci. Res. 24, 201-211 CrossRef PubMed
176. Dyer, C.A. and Benjamins, J.A. (1989) Organization of oligodendroglial membrane sheets: II. Galactocerebroside:antibody interactions signal changes in cytoskeleton and myelin basic protein. J. Neurosci. Res. 24, 212-221 CrossRef PubMed
177. Aggarwal, S., Yurlova, L., Snaidero, N., Reetz, C., Frey, S., Zimmermann, J., Pähler, G., Janshoff, A., Friedrichs, J., Muller, D.J. et al. (2011) A size barrier limits protein diffusion at the cell surface to generate lipid-rich myelin-membrane sheets. Dev. Cell 21, 445-456 CrossRef PubMed
178. Ozgen, H., Schrimpf, W., Hendrix, J., de Jonge, J.C., Lamb, D.C., Hoekstra, D., Kahya, N. and Baron, W. (2014) The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix. PLoS One 9, e101834 CrossRef PubMed
179. Seiberlich, V., Bauer, N.G., Schwarz, L., Ffrench-Constant, C., Goldbaum, O. and Richter-Landsberg, C. (2015) Downregulation of the microtubule associated protein Tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes. Glia 63, 1621-1635 CrossRef PubMed
180. Sobottka, B., Ziegler, U., Kaech, A., Becher, B. and Goebels, N. (2011) CNS live imaging reveals a new mechanism of myelination: the liquid croissant model. Glia 59, 1841-1849 CrossRef PubMed
181. Ioannidou, K., Anderson, K.I., Strachan, D., Edgar, J.M. and Barnett, S.C. (2012) Time-lapse imaging of the dynamics of CNS glial-axonal interactions in vitro and ex vivo. PLoS One 7, e30775 CrossRef PubMed
182. Preston, M.A. and Macklin, W.B. (2015) Zebrafish as a model to investigate CNS myelination. Glia 63, 177-193 CrossRef PubMed
183. Szuchet, S., Nielsen, L.L., Domowicz, M.S., Austin, J.R. and Arvanitis, D.L. (2015) CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process. J. Struct. Biol. 190, 56-72 CrossRef PubMed
184. Gibbs, E.B. and Showalter, S.A. (2015) Quantitative biophysical characterization of intrinsically disordered proteins. Biochemistry 54, 1314-1326 CrossRef PubMed
185. Arvanitis, D.N., Min, W., Gong, Y., Heng, Y.M. and Boggs, J.M. (2005) Two types of detergent-insoluble, glycosphingolipid/cholesterol-rich membrane domains from isolated myelin. J. Neurochem. 94, 1696-1710 CrossRef PubMed
186. DeBruin, L.S., Haines, J.D., Wellhauser, L.A., Radeva, G., Schonmann, V., Bienzle, D. and Harauz, G. (2005) Developmental partitioning of myelin basic protein into membrane microdomains. J. Neurosci. Res. 80, 211-225 CrossRef PubMed
187. DeBruin, L.S., Haines, J.D., Bienzle, D. and Harauz, G. (2006) Partitioning of myelin basic protein into membrane microdomains in a spontaneously demyelinating mouse model for multiple sclerosis. Biochem. Cell Biol. 84, 993-1005 CrossRef PubMed
188. DeBruin, L.S. and Harauz, G. (2007) White matter rafting-membrane microdomains in myelin. Neurochem. Res. 32, 213-228 CrossRef PubMed
189. Gielen, E., Baron, W., Vandeven, M., Steels, P., Hoekstra, D. and Ameloot, M. (2006) Rafts in oligodendrocytes: evidence and structure-function relationship. Glia 54, 499-512 CrossRef PubMed
190. Pritzker, L.B., Joshi, S., Harauz, G. and Moscarello, M.A. (2000) Deimination of myelin basic protein. 2. Effect of methylation of MBP on its deimination by peptidylarginine deiminase. Biochemistry 39, 5382-5388 CrossRef PubMed
191. Harauz, G. and Musse, A.A. (2007) A tale of two citrullines-structural and functional aspects of myelin basic protein deimination in health and disease. Neurochem. Res. 32, 137-158 CrossRef PubMed
192. DeLange, R.J. and Smith, E.L. (1971) Histones: structure and function. Annu. Rev. Biochem. 40, 279-314 CrossRef PubMed
193. Tessarz, P. and Kouzarides, T. (2014) Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol. 15, 703-708 CrossRef PubMed
194. Melters, D.P., Nye, J., Zhao, H. and Dalal, Y. (2015) Chromatin dynamics in vivo: a game of musical chairs. Genes 6, 751-776 CrossRef PubMed
195. Masyuko, R., Lanni, E.J., Sweedler, J.V. and Bohn, P.W. (2013) Correlated imaging-a grand challenge in chemical analysis. Analyst 138, 1924-1939 CrossRef PubMed
196. Christensen, P.C., Brideau, C., Poon, K.W., Doring, A., Yong, V.W. and Stys, P.K. (2014) High-resolution fluorescence microscopy of myelin without exogenous probes. Neuroimage 87, 42-54 CrossRef PubMed
197. Boggs, J.M., Rangaraj, G., Hill, C.M.D., Bates, I.R., Heng, Y.M. and Harauz, G. (2005) Effect of arginine loss in myelin basic protein, as occurs in its deiminated charge isoform, on mediation of actin polymerization and actin binding to a lipid membrane in vitro. Biochemistry 44, 3524-3534 CrossRef PubMed
198. Lee, D.W., Banquy, X., Kristiansen, K., Kaufman, Y., Boggs, J.M. and Israelachvili, J.N. (2014) Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers. Proc. Natl. Acad. Sci. U.S.A. 111, E768-E775 CrossRef PubMed
199. Compston, A. and Coles, A. (2002) Multiple sclerosis. Lancet 359, 1221-1231 CrossRef PubMed
200. Hauser, S.L. and Oksenberg, J.R. (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52, 61-76 CrossRef PubMed
201. Lassmann, H. (2014) Mechanisms of white matter damage in multiple sclerosis. Glia 62, 1816-1830 CrossRef PubMed
202. Yablonskiy, D.A., Luo, J., Sukstanskii, A.L., Iyer, A. and Cross, A.H. (2012) Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 109, 14212-14217 CrossRef PubMed
203. Ohler, B., Graf, K., Bragg, R., Lemons, T., Coe, R., Genain, C., Israelachvili, J. and Husted, C. (2004) Role of lipid interactions in autoimmune demyelination. Biochim. Biophys. Acta 1688, 10-17 CrossRef PubMed
204. Husted, C. and Dhondup, L. (2009) Tibetan medical interpretation of myelin lipids and multiple sclerosis. Ann. N.Y. Acad. Sci. 1172, 278-296 CrossRef PubMed
205. Wood, D.D. and Moscarello, M.A. (1997) Molecular biology of the glia: components of myelin-myelin basic protein-the implication of post-translational changes for demyelinating disease. In Molecular Biology of Multiple Sclerosis (Russell, W.C., ed.), pp. 37-54, John Wiley and Sons, Chichester
206. Kim, J.K., Mastronardi, F.G., Wood, D.D., Lubman, D.M., Zand, R. and Moscarello, M.A. (2003) Multiple sclerosis: an important role for post-translational modifications of myelin basic protein in pathogenesis. Mol. Cell. Proteomics 2, 453-462 PubMed
207. Moscarello, M.A., Mastronardi, F.G. and Wood, D.D. (2007) The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis. Neurochem. Res. 32, 251-256 CrossRef PubMed
208. Musse, A.A., Li, Z., Ackerley, C.A., Bienzle, D., Lei, H., Poma, R., Harauz, G., Moscarello, M.A. and Mastronardi, F.G. (2008) Peptidylarginine deiminase 2 (PAD2) expression in a transgenic mouse leads to specific central nervous system (CNS) myelin instability. Dis. Models Mech. 1, 229-240 CrossRef
209. Moscarello, M.A. (1976) Chemical and physical properties of myelin proteins. In Current Topics in Membranes and Transport (Bronner, F. and Kleinzeller, A., eds), pp. 1-28, Academic Press, San Diego CrossRef
210. Finch, P.R., Wood, D.D. and Moscarello, M.A. (1971) The presence of citrulline in a myelin protein fraction. FEBS Lett. 15, 145-148 CrossRef PubMed
211. Moscarello, M.A., Wood, D.D., Ackerley, C. and Boulias, C. (1994) Myelin in multiple sclerosis is developmentally immature. J. Clin. Invest. 94, 146-154 CrossRef PubMed
212. Wood, D.D., Bilbao, J.M., O'Connors, P. and Moscarello, M.A. (1996) Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein. Ann. Neurol. 40, 18-24 CrossRef PubMed
213. McLaurin, J., Ackerley, C.A. and Moscarello, M.A. (1993) Localization of basic proteins in human myelin. J. Neurosci. Res. 35, 618-628 CrossRef PubMed
214. Cao, L., Goodin, R., Wood, D., Moscarello, M.A. and Whitaker, J.N. (1999) Rapid release and unusual stability of immunodominant peptide 45-89 from citrullinated myelin basic protein. Biochemistry 38, 6157-6163 CrossRef PubMed
215. Musse, A.A. and Harauz, G. (2007) Molecular "negativity" may underlie multiple sclerosis: role of the myelin basic protein family in the pathogenesis of MS. Int. Rev. Neurobiol. 79, 149-172 CrossRef PubMed
216. Sospedra, M. and Martin, R. (2005) Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683-747 CrossRef PubMed
217. Frid, K., Einstein, O., Friedman-Levi, Y., Binyamin, O., Ben-Hur, T. and Gabizon, R. (2015) Aggregation of MBP in chronic demyelination. Ann. Clin. Transl. Neurol. 2, 711-721 CrossRef PubMed
218. Smith, G.S.T., Paez, P.M., Spreuer, V., Campagnoni, C.W., Boggs, J.M., Campagnoni, A.T. and Harauz, G. (2011) Classical 18.5-and 21.5-kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms. J. Neurosci. Res. 89, 467-480 CrossRef PubMed
219. Musse, A.A., Polverini, E., Raijmakers, R. and Harauz, G. (2008) Kinetics of human peptidylarginine deiminase 2 (hPAD2)-reduction of Ca2+-dependence by phospholipids and assessment of proposed inhibition by paclitaxel side chains. Biochem. Cell Biol. 86, 437-447 CrossRef PubMed
220. Wood, D.D., Ackerley, C.A., Brand, B., Zhang, L., Raijmakers, R., Mastronardi, F.G. and Moscarello, M.A. (2008) Myelin localization of peptidylarginine deiminases 2 and 4: comparison of PAD2 and PAD4 activities. Lab. Invest. 88, 354-364 CrossRef PubMed
221. Slade, D.J., Fang, P., Dreyton, C.J., Zhang, Y., Fuhrmann, J., Rempel, D., Bax, B.D., Coonrod, S.A., Lewis, H.D., Guo, M. et al. (2015) Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design. ACS Chem. Biol. 10, 1043-1053 CrossRef PubMed
222. Barnett, M.H. and Prineas, J.W. (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann. Neurol. 55, 458-468 CrossRef PubMed
223. Trapp, B.D. and Nave, K.A. (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci. 31, 247-269 CrossRef PubMed
224. Lassmann, H. and van Horssen, J. (2011) The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 585, 3715-3723 CrossRef PubMed
225. Lassmann, H. (2013) Pathology and disease mechanisms in different stages of multiple sclerosis, J. Neurol. Sci. 333, 1-4 CrossRef
226. Henderson, A.P., Barnett, M.H., Parratt, J.D. and Prineas, J.W. (2009) Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann. Neurol. 66, 739-753 CrossRef PubMed
227. Tsutsui, S. and Stys, P.K. (2009) Degeneration versus autoimmunity in multiple sclerosis. Ann. Neurol. 66, 711-713 CrossRef PubMed
228. Stys, P.K., Zamponi, G.W., van Minnen, J. and Geurts, J.J.G. (2012) Will the real multiple sclerosis please stand up? Nat. Rev. Neurosci. 13, 507-514 CrossRef PubMed
229. Stys, P.K. (2013) Pathoetiology of multiple sclerosis: are we barking up the wrong tree? F1000Prime Rep. 5, 20 CrossRef PubMed
230. Lassmann, H., Bruck, W. and Lucchinetti, C. (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol. Med. 7, 115-121 CrossRef PubMed
231. Bush, W.S., Sawcer, S.J., De Jager, P.L., Oksenberg, J.R., McCauley, J.L., Pericak-Vance, M.A. and Haines, J.L. (2010) Evidence for polygenic susceptibility to multiple sclerosis-the shape of things to come. Am. J. Hum. Genet. 86, 621-625 CrossRef PubMed
232. Baranzini, S.E., Khankhanian, P., Patsopoulos, N.A., Li, M., Stankovich, J., Cotsapas, C., Søndergaard, H.B., Ban, M., Barizzone, N., Bergamaschi, L. et al. (2013) Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 3,000 controls. Am. J. Hum. Genet. 92, 854-865 CrossRef PubMed
233. Chafe, R., Born, K.B., Slutsky, A.S. and Laupacis, A. (2011) The rise of people power. Nature 472, 410-411 CrossRef PubMed
234. Baracchini, C., Atzori, M. and Gallo, P. (2013) CCSVI and MS: no meaning, no fact. Neurol. Sci. 34, 269-279 CrossRef PubMed
235. Husted, C.A., Goodin, D.S., Hugg, J.W., Maudsley, A.A., Tsuruda, J.S., de Bie, S.H., Fein, G., Matson, G.B. and Weiner, M.W. (1994) Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging. Ann. Neurol. 36, 157-165 CrossRef PubMed
236. de Groot, M., Verhaaren, B.F., de Boer, R., Klein, S., Hofman, A., van der Lugt, A., Ikram, M.A., Niessen, W.J. and Vernooij, M.W. (2013) Changes in normal-appearing white matter precede development of white matter lesions. Stroke 44, 1037-1042 CrossRef PubMed
237. Tuller, T., Atar, S., Ruppin, E., Gurevich, M. and Achiron, A. (2011) Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions. Hum. Mol. Genet. 20, 3606-3619 CrossRef PubMed
238. Han, M.H. and Steinman, L. (2009) Systems biology for identification of molecular networks in multiple sclerosis. Mult. Scler. 15, 529-530 CrossRef PubMed
239. Tsutsui, S. and Stys, P.K. (2013) Metabolic injury to axons and myelin. Exp. Neurol. 246, 26-34 CrossRef PubMed
240. Tejada-Simon, M.V., Zang, Y.C., Hong, J., Rivera, V.M. and Zhang, J.Z. (2003) Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann. Neurol. 53, 189-197 CrossRef PubMed
241. Kakalacheva, K., Munz, C. and Lunemann, J.D. (2011) Viral triggers of multiple sclerosis. Biochim. Biophys. Acta 1812, 132-140 CrossRef PubMed
242. Wuest, S.C., Mexhitaj, I., Chai, N.R., Romm, E., Scheffel, J., Xu, B., Lane, K., Wu, T. and Bielekova, B. (2014) A complex role of herpes viruses in the disease process of multiple sclerosis. PLoS One 9, e105434 CrossRef PubMed
243. Fujinami, R.S. and Oldstone, M.B. (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230, 1043-1045 CrossRef PubMed
244. Shaw, S.Y., Laursen, R.A. and Lees, M.B. (1986) Analogous amino acid sequences in myelin proteolipid and viral proteins. FEBS Lett. 207, 266-270 CrossRef PubMed
245. Tait, A.R. and Straus, S.K. (2008) Phosphorylation of U24 from human Herpes virus type 6 (HHV-6) and its potential role in mimicking myelin basic protein (MBP) in multiple sclerosis. FEBS Lett. 582, 2685-2688 CrossRef PubMed
246. Sang, Y., Tait, A.R., Scott, W.R., Creagh, A.L., Kumar, P., Haynes, C.A. and Straus, S.K. (2014) Probing the interaction between U24 and the SH3 domain of fyn tyrosine kinase. Biochemistry 53, 6092-6102 CrossRef PubMed
247. Bello-Morales, R., Fedetz, M., Alcina, A., Tabares, E. and Lopez-Guerrero, J.A. (2005) High susceptibility of a human oligodendroglial cell line to herpes simplex type 1 infection. J. Neurovirol. 11, 190-198 CrossRef PubMed
248. Dietrich, J., Blumberg, B.M., Roshal, M., Baker, J.V., Hurley, S.D., Mayer-Proschel, M. and Mock, D.J. (2004) Infection with an endemic human herpesvirus disrupts critical glial precursor cell properties. J. Neurosci. 24, 4875-4883 CrossRef PubMed
249. Mock, D.J., Strathmann, F., Blumberg, B.M. and Mayer-Proschel, M. (2006) Infection of murine oligodendroglial precursor cells with Human Herpesvirus 6 (HHV-6):establishment of a murine in vitro model. J. Clin. Virol. 37 (Suppl. 1), S17-S23 CrossRef PubMed
250. Morgan, A.A. and Rubenstein, E. (2013) Proline: the distribution, frequency, positioning, and common functional roles of proline and polyproline sequences in the human proteome. PLoS One 8, e53785 CrossRef PubMed
251. Peil, L., Starosta, A.L., Lassak, J., Atkinson, G.C., Virumae, K., Spitzer, M., Tenson, T., Jung, K., Remme, J. and Wilson, D.N. (2013) Distinct XPPX sequence motifs induce ribosome stalling, which is rescued by the translation elongation factor EF-P. Proc. Natl. Acad. Sci. U.S.A. 110, 15265-15270 CrossRef PubMed
252. Darnell, J.C. and Klann, E. (2013) The translation of translational control by FMRP: therapeutic targets for FXS. Nat. Neurosci. 16, 1530-1536 CrossRef PubMed
253. Darnell, J.C., Van Driesche, S.J., Zhang, C., Hung, K.Y., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W. et al. (2011) FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247-261 CrossRef PubMed
254. Adzhubei, A.A., Sternberg, M.J. and Makarov, A.A. (2013) Polyproline-II helix in proteins: structure and function. J. Mol. Biol. 425, 2100-2132 CrossRef PubMed
255. Wulf, G., Finn, G., Suizu, F. and Lu, K.P. (2005) Phosphorylation-specific prolyl isomerization: is there an underlying theme? Nat. Cell Biol. 7, 435-441 CrossRef PubMed
256. Liou, Y.C., Zhou, X.Z. and Lu, K.P. (2011) Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins. Trends Biochem. Sci. 36, 501-514 CrossRef PubMed
257. Nygaard, E., Mendz, G.L., Moore, W.J. and Martenson, R.E. (1984) NMR of a peptic peptide spanning the triprolyl sequence in myelin basic protein. Biochemistry 23, 4003-4010 CrossRef
258. Fraser, P.E. and Deber, C.M. (1985) Structure and function of the proline-rich region of myelin basic protein. Biochemistry 24, 4593-4598 CrossRef PubMed
259. Kelly, M.A., Chellgren, B.W., Rucker, A.L., Troutman, J.M., Fried, M.G., Miller, A.F. and Creamer, T.P. (2001) Host-guest study of left-handed polyproline II helix formation. Biochemistry 40, 14376-14383 CrossRef PubMed
260. Rubenstein, E. (2008) Misincorporation of the proline analog azetidine-2-carboxylic acid in the pathogenesis of multiple sclerosis: a hypothesis. J. Neuropathol. Exp. Neurol. 67, 1035-1040 CrossRef PubMed
261. Rubenstein, E., McLaughlin, T., Winant, R.C., Sanchez, A., Eckart, M., Krasinska, K.M. and Chien, A. (2009) Azetidine-2-carboxylic acid in the food chain. Phytochemistry 70, 100-104 CrossRef PubMed
262. Bessonov, K., Vassall, K.A. and Harauz, G. (2013) Parameterization of the proline analogue Aze (azetidine-2-carboxylic acid) for molecular dynamics simulations and evaluation of its effect on homo-pentapeptide conformations. J. Mol. Graph. Model. 39, 118-125 CrossRef PubMed
263. Uversky, V.N. (2014) The triple power of D(3): protein intrinsic disorder in degenerative diseases. Front. Biosci. (Landmark Ed.) 19, 181-258 CrossRef PubMed
264. Jeganathan, S., von Bergen, M., Mandelkow, E.M. and Mandelkow, E. (2008) The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments. Biochemistry 47, 10526-10539 CrossRef PubMed
265. Yu, J. and Lyubchenko, Y.L. (2009) Early stages for Parkinson's development: alpha-synuclein misfolding and aggregation. J. Neuroimmune Pharmacol. 4, 10-16 CrossRef PubMed
266. Zamponi, G.W. and Stys, P.K. (2009) Role of prions in neuroprotection and neurodegeneration: a mechanism involving glutamate receptors? Prion 3, 187-189 CrossRef PubMed
267. Arya, S. and Mukhopadhyay, S. (2014) Ordered water within the collapsed globules of an amyloidogenic intrinsically disordered protein. J. Phys. Chem. B 118, 9191-9198 CrossRef PubMed
268. Wong, J.H., Halliday, G.M. and Kim, W.S. (2014) Exploring myelin dysfunction in multiple system atrophy. Exp. Neurobiol. 23, 337-344 CrossRef PubMed
269. Richter-Landsberg, C. (2015) Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the Intersection of neuroprotection and neurodegeneration. Biol. Chem., doi:10.1515/hsz-2015-0157 PubMed
270. Dobson, C.M. (1999) Protein misfolding, evolution and disease. Trends Biochem. Sci. 24, 329-332 CrossRef PubMed
271. Jain, N., Bhattacharya, M. and Mukhopadhyay, S. (2011) Chain collapse of an amyloidogenic intrinsically disordered protein. Biophys. J. 101, 1720-1729 CrossRef PubMed
272. Mukrasch, M.D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E. and Zweckstetter, M. (2009) Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol. 7, e34 CrossRef PubMed
273. Torbeev, V.Y. and Hilvert, D. (2013) Both the cis-trans equilibrium and isomerization dynamics of a single proline amide modulate beta2-microglobulin amyloid assembly. Proc. Natl. Acad. Sci. U.S.A. 110, 20051-20056 CrossRef PubMed
274. Barman, A. and Hamelberg, D. (2014) Loss of intramolecular electrostatic interactions and limited conformational ensemble may promote self-association of cis-tau peptide. Proteins 83, 436-444 CrossRef PubMed
275. Pappu, R.V., Wang, X., Vitalis, A. and Crick, S.L. (2008) A polymer physics perspective on driving forces and mechanisms for protein aggregation. Arch. Biochem. Biophys. 469, 132-141 CrossRef PubMed
276. Li, P., Banjade, S., Cheng, H.C., Kim, S., Chen, B., Guo, L., Llaguno, M., Hollingsworth, J.V., King, D.S., Banani, S.F. et al. (2012) Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336-340 CrossRef PubMed