Divalent metals of myelin and their differential binding by myelin basic protein of bovine central nervous system

Berlet, Hans H.; Bischoff, Heike; Weinhardt, F.

doi:10.1016/0304-3940(94)90938-5

Cited by 29 publications

(12 citation statements)

References 18 publications

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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: 77%

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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Section: Biochemical Analysis: Enrichment Of Specific Lipidsmentioning

confidence: 77%

Multilamellar packing of myelin modeled by lipid-bound MBP

Riccio¹,

Fasano²,

Borenshtein³

et al. 2000

J. Neurosci. Res.

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“…The requirement of Mn 2ϩ for efficient binding of the intact ␣ M ␤ 2 receptor to GA and MBP indicates a type of conformational regulation of integrin binding, which involves transmission of conformational changes through the receptor (52) and ultimately leads to the conformational changes in the I domain that enables ligand recognition. We cannot exclude secondary effects of the application of Mn 2ϩ to the experiments, although MBP was found not to bind Mn 2ϩ (53). To test the influence of integrin conformation by another strategy, we showed that binding by MNCs as well as monocytes was also induced by the addition of a mAb (28) that activates ␤ 2 integrins for ligand binding; this finding clearly suggests that integrin conformational changes are required for the ␣ M ␤ 2 receptor to bind MBP and that the primary effect of Mn 2ϩ like the Ab is to favor the integrin ligand-binding conformation.…”

Section: Discussionmentioning

confidence: 92%

Structural Insight into the Function of Myelin Basic Protein as a Ligand for Integrin αMβ2

Stapulionis¹,

Oliveira

Gjelstrup³

et al. 2008

The Journal of Immunology

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Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate mimics the conformationally labile regions of MBP, interacts in the unfolded state strongly with αMβ2, and inhibits the MBP binding to αMβ2. Our study reveals a link between MBP, glatiramer acetate, and the αMβ2 integrin, and suggests a new model for MS pathogenesis based on the recognition of unfolded MBP by the αMβ2 integrin.

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“…We know that the concentration of zinc in myelin (about 50 mM) is substantially higher than that of any other trace element (Altman and Dittmer, 1973;Iyengar et al, 1978), that zinc plays a role in many neurological disorders such as MS (Ho et al, 1986), and that zinc specifically binds to and stabilises the association of MBP to the CNS myelin membrane, i.e. is physiologically significant (Earl et al, 1988;Liuzzi et al, 1991;Berlet et al, 1994;Cavatorta et al, 1994;Riccio et al, 1995;Tsang et al, 1997;Nuzzo et al, 2002). Again for structural purposes, there are numerous examples of divalent cation-binding stabilising folds of other IUPs, e.g.…”

Section: Mbp Binds Various Small Ligandsmentioning

confidence: 97%

“…Cd 2þ . Co 2þ in decreasing order of affinity (Berlet et al, 1994). It also binds serotonin and some hallucinogenic drugs (Alivisatos et al, 1971;Carnegie et al, 1972), heme (Vacher et al, 1984;Morris et al, 1987), azo dyes (Liebes et al, 1976), and GTP (Chan et al, 1988).…”

Section: Mbp Binds Various Small Ligandsmentioning

confidence: 99%