Myelin basic protein interaction with zinc and phosphate: fluorescence studies on the water-soluble form of the protein

Cavatorta, P.; Giovanelli, S.; Bobba, Antonella; Riccio, P.; Szabo, Arthur G.; Quagliariello, E

doi:10.1016/s0006-3495(94)80899-9

Cited by 34 publications

(31 citation statements)

References 23 publications

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“…Light scattering distortions due to aggregation and CD spectrum flattening would affect the estimates of secondary structure content. However, in our experience, this phenomenon has not been significant even when the MBP has been strongly aggregated (87). Here, we consider that the calculated proportions of secondary structure would still be accurate for this relatively low lipid:protein ratio.…”

Section: Circular Dichroism Of Mbp Preparationsmentioning

confidence: 77%

Characterization of a Recombinant Murine 18.5-kDa Myelin Basic Protein

Bates

Matharu

Ishiyama

et al. 2000

Protein Expression and Purification

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Section: Circular Dichroism Of Mbp Preparationsmentioning

confidence: 77%

Characterization of a Recombinant Murine 18.5-kDa Myelin Basic Protein

Bates

Matharu

Ishiyama

et al. 2000

Protein Expression and Purification

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“…It also interacts with other proteins such as proteolipid protein (67,68), calmodulin (12), actin (51), and tubulin (52) and sequesters zinc (72). Thus, it is not unexpected that MBP forms extensive clusters on negatively charged lipid monolayers, especially in the low salt buffer G (Fig.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional Structure of Myelin Basic Protein

Beniac

Luckevich

Czarnota

et al. 1997

Journal of Biological Chemistry

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Myelin basic protein (MBP) plays an integral role in the structure and function of the myelin sheath. In humans and cattle, an 18.5-kDa isoform of MBP predominates and exists as a multitude of charge isomers resulting from extensive and varied post-translational modifications. We have purified the least modified isomer (named C1) of the 18.5-kDa isoform of MBP from fresh bovine brain and imaged this protein as negatively stained single particles adsorbed to a lipid monolayer. Under these conditions, MBP/C1 presented diverse projections whose relative orientations were determined using an iterative quaternion-assisted angular reconstitution scheme. In different buffers, one with a low salt and the other with a high salt concentration, the conformation of the protein was slightly different. In low salt buffer, the three-dimensional reconstruction, solved to a resolution of 4 nm, had an overall "C" shape of outer radius 5.5 nm, inner radius 3 nm, overall circumference 15 nm, and height 4.7 nm. The three-dimensional reconstruction of the protein in high salt buffer, solved to a resolution of 2.8 nm, was essentially the same in terms of overall dimensions but had a somewhat more compact architecture. These results are the first structures achieved directly for this unusual macromolecule, which plays a key role in the development of multiple sclerosis.The myelin sheath is a multilamellar membranous structure that surrounds the axons of the central and peripheral nervous systems (1-3). Proteins constitute 30% of the dry weight of central nervous system myelin, with the major ones being proteolipid protein (or lipophilin; 50% of total protein) and myelin basic protein (MBP; 1 20% of total protein) (1-5). Myelin basic protein-lipid interaction has been shown to be critical for the formation and stability of the multilamellar myelin sheath (6 -8), although the physicochemical mechanisms by which this occurs are still not clearly defined despite many investigations (e.g. Refs. 9 -28). Myelin basic protein was the first agent in brain or spinal cord homogenates discovered to be responsible for experimental allergic encephalomyelitis, which is considered to be an animal model for the human disease multiple sclerosis (29 -31).In all species studied, MBP exists in a number of isoforms as a result of differential splicing of its primary mRNA transcript (32-34). The 18.5-kDa isoform is the most common in mammals, including humans and cattle. The amino acid sequences of the 18.5-kDa isoforms of human and bovine MBP were reported independently by Carnegie et al. (29) and by Eylar et al. (30), respectively. Briefly, MBP contains (i) no cysteinyl residues, (ii) 12 lysyl and 19 arginyl residues giving it a highly basic character (pI ϳ10.6), (iii) 11 prolyl residues (including a triproline repeat adjacent to human Thr 98 and bovine Thr 97 ), (iv) a mitogen-activated protein kinase site (35), and (v) a large number of seryl and threonyl residues making it an excellent substrate for several other protein kinases (36 -38). Phosphorylat...

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“…Also, we determined whether maintaining zinc ions in the final dialysis medium would affect the lipid composition of the lipid-bound MBP aggregates. Zinc ions are thought to stabilize myelin structure possibly via interactions with MBP (Inouye and Kirschner, 1984;Earl et al, 1988;Berlet et al, 1994;Riccio et al, 1995) and have been shown to promote the aggregation of MBP (Cavatorta et al, 1994). Analysis of the lipid composition of lipid-bound MBP dialyzed against 0.5 mM zinc acetate at pH 7.5 (rather than deionized water) did not, however, reveal any differences in either polar or neutral lipids that were associated with the MBP (Fig.…”

Section: Biochemical Analysis: Enrichment Of Specific Lipidsmentioning

confidence: 94%

Multilamellar packing of myelin modeled by lipid-bound MBP

Riccio¹,

Fasano²,

Borenshtein³

et al. 2000

J. Neurosci. Res.

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Membrane compaction and adhesion at the major dense line (cytoplasmic apposition) of myelin, particularly in the central nervous system (CNS), is typically attributed to myelin basic protein (MBP). To explore the role of MBP in myelin membrane adhesion, we attempted to reconstitute the major dense line of myelin from purified lipid-bound MBP, which is a detergent-soluble form of MBP that retains the binding of all the myelin lipids. Removal of detergent by long-term dialysis yielded a precipitate, which, when analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and thin-layer chromatography, contained MBP that was still associated with myelin lipids, but in different proportions than in the native membrane. Comparison of lipid composition among isolated myelin, MBP-free myelin lipids, and lipid-bound MBP aggregates showed that the lipid-bound form of the protein was specifically enriched in phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, phosphatidylinositol, and phosphatidylserine. Electron microscopy and x-ray diffraction demonstrated that the lipid-MBP complexes formed multilayers having periods of 70-85 A, which correspond in width to individual myelin membranes. By contrast, the lipids alone assembled as multilayers having a period of approximately 40 A. Thus, the detergent-soluble form of MBP, which is bound to lipids, might serve as a simple model for the cytoplasmic apposition of myelin.

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Myelin basic protein interaction with zinc and phosphate: fluorescence studies on the water-soluble form of the protein

Cited by 34 publications

References 23 publications

Characterization of a Recombinant Murine 18.5-kDa Myelin Basic Protein

Characterization of a Recombinant Murine 18.5-kDa Myelin Basic Protein

Three-dimensional Structure of Myelin Basic Protein

Multilamellar packing of myelin modeled by lipid-bound MBP

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