Electron Microscopy of Myelin Basic Protein (MBP) Organized as Planar Arrays on a Lipid Monolayer Surface: Deimination of MBP Hinders Its Organizational Properties

2000 ◽  
Vol 6 (S2) ◽  
pp. 250-251
Author(s):  
N. Ishiyama ◽  
P. Matharu ◽  
I.R. Bates ◽  
D.D. Wood ◽  
M.A. Moscarello ◽  
...  

Myelin basic protein (MBP) is one of the principal constituents of the mammalian myelin sheath. It is a basic peripheral membrane protein in the major dense line and is believed to play a structural role in maintaining myelin stability through its close association with lipids and other proteins. Immune responses to MBP have been implicated in the pathogenesis of multiple sclerosis (MS), the most common autoimmune disease of the central nervous system in North America and Northern Europe. The correlation between the severity of MS and the deimination of arginyl to citrullinyl residues in MBP was well illustrated in the acute case of MS (Marburg type) that contained MBP with 18 out of 19 arginines citrullinated.We have studied a recombinant hexahistidine-tagged murine MBP (rmMBP, 18.5 kDa isoform) by electron microscopy of the protein organized as planar arrays on lipid monolayers that consisted of the nickel chelating lipid, l,2-dioleoyl-.yn-glycero-3-[(N(5-amino-l-carboxypentyl)iminodiacetic acid)succinyl] (Nickel salt) (Ni2+-NTADOGS), and the filler lipid, liver phosphatidylinositol (PI).

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 529 ◽  
Author(s):  
Jennica Träger ◽  
Katharina Widder ◽  
Andreas Kerth ◽  
George Harauz ◽  
Dariush Hinderberger

Myelin basic protein (MBP) is located in the insulating covers of nerve cells in the brain and spinal cord. By interacting with lipid membranes, it is responsible for compaction of the myelin sheath in the central nervous system, which is weakened in demyelinating diseases. The lipid composition of the myelin leaflet has a high impact on the interaction between the membrane and MBP. Cholesterol is present in the cytoplasmic leaflet with a rather high amount of 44% (mol%). In this study, the focus is on the effect of cholesterol, mainly by varying its content, on the interaction of MBP with a lipid monolayer. Therefore, Langmuir lipid monolayers mimicking the cytoplasmic membrane of myelin and monolayers with variations of cholesterol content between 0% and 100% were measured at the air/water interface with additional imaging by fluorescence microscopy. All experiments were performed with and without bovine MBP to study the dependence of the interaction of the protein with the monolayers on the cholesterol content. The native amount of 44% cholesterol in the monolayer combines optima in the order of the monolayer (presumably correlating to compaction and thermodynamic stability) and protein interaction and shows unique features in comparison to lower or higher cholesterol contents.


2010 ◽  
Vol 88 (2) ◽  
pp. 143-155 ◽  
Author(s):  
David S. Libich ◽  
Mumdooh A.M. Ahmed ◽  
Ligang Zhong ◽  
Vladimir V. Bamm ◽  
Vladimir Ladizhansky ◽  
...  

The classic 18.5 kDa isoform of myelin basic protein (MBP) is central to maintaining the structural homeostasis of the myelin sheath of the central nervous system. It is an intrinsically disordered, promiscuous, multifunctional, peripheral membrane protein, whose conformation adapts to its particular environment. Its study requires the selective and complementary application of diverse approaches, of which solution and solid-state NMR spectroscopy are the most powerful to elucidate site-specific features. We review here several recent solution and solid-state NMR spectroscopic studies of 18.5 kDa MBP, and the induced partial disorder-to-order transitions that it has been demonstrated to undergo when complexed with calmodulin, actin, and phospholipid membranes.


1998 ◽  
Vol 187 (9) ◽  
pp. 1543-1548 ◽  
Author(s):  
Anna Lobell ◽  
Robert Weissert ◽  
Maria K. Storch ◽  
Cecilia Svanholm ◽  
Katrien L. de Graaf ◽  
...  

We explore here if vaccination with DNA encoding an autoantigenic peptide can suppress autoimmune disease. For this purpose we used experimental autoimmune encephalomyelitis (EAE), which is an autoaggressive disease in the central nervous system and an animal model for multiple sclerosis. Lewis rats were vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig myelin basic protein peptide 68–85 (MBP68–85), before induction of EAE with MBP68–85 in complete Freund's adjuvant. Compared to vaccination with a control DNA construct, the vaccination suppressed clinical and histopathological signs of EAE, and reduced the interferon γ production after challenge with MBP68–85. Targeting of the gene product to Fc of IgG was essential for this effect. There were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding autoantigenic peptides may be useful tools in controlling autoimmune disease.


1990 ◽  
Vol 10 (1) ◽  
pp. 55-59
Author(s):  
Tiziana Bellini ◽  
Diana Degani ◽  
Maurizio Matteuzzi ◽  
Franco Dallocchio

Myelin Basic Protein, one of the major membrane protein component of the central nervous system, was used to probe the molecular mechanism of cellular activation by phytohaemagglutinin. Pre-treatment of human lymphocytes with myelin basic protein results in a lower rising of cytosolic concentration of free calcium after stimulation with phytohaemagglutinin. This effect is dependent on myelin basic protein concentration and on the preincubation time of the protein with the cells. It is not due to a interaction between myelin basic protein and phytohaemagglutinin, but appears to be a consequence of the binding of the protein to the cell surface. The reduction of the rise of cytosolic calcium induced by phytohaemagglutinin is specific for the myelin basic protein because other proteins like albumin and protamine have no effect.


Author(s):  
Kostrikina IA ◽  
◽  
Granieri E ◽  
Nevinsky GA ◽  
◽  
...  

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.


2011 ◽  
Vol 192 (5) ◽  
pp. 797-811 ◽  
Author(s):  
Lisbeth S. Laursen ◽  
Colin W. Chan ◽  
Charles ffrench-Constant

Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation of protein synthesis represents one mechanism used to control the different requirements for myelin sheath at each axo–glia interaction. Prior work has established that β1-integrins are involved in the axoglial interactions that initiate myelination. Here, we show that integrin activation regulates translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3′UTR. During oligodendrocyte differentiation and myelination α6β1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin sheath. Furthermore, knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Together, these results identify a novel pathway by which axoglial adhesion molecules coordinate MBP synthesis with myelin sheath formation.


2002 ◽  
Vol 8 (S02) ◽  
pp. 834-835
Author(s):  
C. M. Hill ◽  
I. R. Bates ◽  
C. E. Antler ◽  
G. F. White ◽  
F. R. Hallett ◽  
...  

2017 ◽  
Vol 38 (6) ◽  
pp. 1047-1059 ◽  
Author(s):  
Joanne O Davidson ◽  
Vittoria Draghi ◽  
Sean Whitham ◽  
Simerdeep K Dhillon ◽  
Guido Wassink ◽  
...  

The optimal duration of mild “therapeutic” hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation. Hypothermia for 48 h was associated with improved outcomes compared to normothermia, but a progressive deterioration of EEG power after rewarming compared to 72 h of hypothermia, with impaired neuronal survival and myelin basic protein, and more microglia in the white matter and cortex. These findings show that head cooling for 48 h is partially neuroprotective, but is inferior to cooling for 72 h after cerebral ischemia in fetal sheep. The close association between rewarming at 48 h, subsequent deterioration in EEG power and increased cortical inflammation strongly suggests that deleterious inflammation can be reactivated by premature rewarming.


2021 ◽  
Author(s):  
Lei Zhang ◽  
Ming Zhang ◽  
Runguang Sun

Abstract The interaction between the role of 18.5 KDa myelin basic protein (MBP) isoform and phospholipids has been thought to maintain the stability and compactness of the myelin sheath structure. In this study, we describe the statistical thermodynamic theory of different concentrations’ effects on MBP in the major myelin lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE),and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS)) monolayers at the air/subphase interface via Langmuir-Blodgett (LB) technique. A simple statistical mechanical theory is established that predicts the interaction between proteins and phosphate head groups at low surface pressures and the second virial coefficient dependences for the PC, PE, and PS head groups are illustrated. In addition, the surface pressure(π)-mean molecular area(mma) curves were also analyzed using two-dimensional virial equation of state (2D-VES). The positively charged showed that MBP may integrate into different lipid monolayers via hydrophobic and electrostatic interactions, which was found to be consistent with AFM observations of domain and aggregate structures as well as with changes in the surface morphology induced by MBP. These analyses pertaining to membrane structure will provide better insight into membrane modeling systems, especially the interaction between membrane molecules.


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