Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles

Mendz, George L.; Brown, L. R.; Martenson, Russell E.

doi:10.1021/bi00461a014

Cited by 35 publications

(30 citation statements)

References 38 publications

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“…Segment mMBP (38 -49) has neither a hydrophobic nor a hydrophilic face indicative of an amphipathic ␣-helix. In contrast, segment mMBP-(82-93) is strongly amphipathic with very hydrophobic amino acids (Val, Phe, and Ile) on one side and polar amino acids (Lys, Thr, His, and Asn) on the other side of the ␣-helix (a similar prediction has been noted previously (46,47)). The segment mMBP-(82-93) has a hydrophobic-hydrophilic residue ratio of 13:5, which in peptides has been shown to result in immersion of their hydrophobic regions into lipid bilayers (48).…”

Section: Labeled Mbp Sites Are Not Sequestered In Aqueous Solution-supporting

confidence: 71%

Membrane-anchoring and Charge Effects in the Interaction of Myelin Basic Protein with Lipid Bilayers Studied by Site-directed Spin Labeling

Bates

Boggs

Feix

et al. 2003

Journal of Biological Chemistry

112

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Myelin basic protein (MBP) maintains the compaction of the myelin sheath in the central nervous system by anchoring the cytoplasmic face of the two apposing bilayers and may also play a role in signal transduction. Site-directed spin labeling was done at eight matching sites in each of two recombinant murine MBPs, qC1 (charge ؉19) and qC8 charge (؉13), which, respectively, emulate the native form of the protein (C1) and a posttranslationally modified form (C8) that is increased in multiple sclerosis. When interacting with large unilamellar vesicles, most spin-labeled sites in qC8 were more mobile than those in qC1. Depth measurement via continuous wave power saturation indicated that the Nterminal and C-terminal sites in qC1 were located below the plane of the phospholipid headgroups. In qC8, the C-terminal domain dissociated from the membrane, suggesting a means by which the exposure of natural C8 to cytosolic enzymes and ligands might increase in vivo in multiple sclerosis. The importance of two Phe-Phe pairs in MBP to its interactions with lipids was investigated by separately mutating each pair to Ala-Ala. The mobility at F42A/F43A and especially F86A/F87A increased significantly. Depth measurements and helical wheel analysis indicated that the Phe-86/Phe-87 region could form a surface-seeking amphipathic ␣-helix.The 18.5-kDa isoform of myelin basic protein (MBP) 1 is a stabilizing factor in the myelin sheath. A major function of MBP is to bind to the apposing cytoplasmic faces of the myelin membrane and maintain compaction for efficient nerve transmission (1, 2), but it may also be involved in signal transduction (3). Because of a diversity of post-translational modifications, MBP exists as a number of charge isomers denoted C1-C8 with a net positive charge decreasing from ϩ19 to ϩ13 at pH 7.0 (4 -6). The C8 component is characterized by the enzymatic deimination of arginine to citrulline. Each conversion results in the loss of one positive charge, and C8 is thus the least basic form of the protein and has a diminished ability to cause adhesion of lipid bilayers (7-9). Component C8 occurs in greater amounts in patients with the demyelinating disease, multiple sclerosis (9, 10).We have previously produced and characterized a recombinant murine 18.5-kDa MBP (11). Here, we will denote this protein quasi-C1 (qC1), because it is unmodified post-translationally (with the exception of an LEH 6 tag) and emulates the least-modified, most basic charge isomer C1. We have also generated by site-directed mutagenesis a quasi-deiminated form of recombinant murine 18.5-kDa MBP that we call qC8, since it was designed to mimic the less cationic natural form C8. The recombinant qC8 consists of Arg/Lys 3 Gln substitutions at the same deimination sites in human MBP that predominate in chronic multiple sclerosis and has properties similar to those of natural C8 (7). The net charge of qC1 is ϩ19 at neutral pH, whereas that of qC8 is ϩ13 as for their natural counterparts.In this study, we investigated the electrostatic and hydro...

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Section: Labeled Mbp Sites Are Not Sequestered In Aqueous Solution-supporting

confidence: 71%

Membrane-anchoring and Charge Effects in the Interaction of Myelin Basic Protein with Lipid Bilayers Studied by Site-directed Spin Labeling

Bates

Boggs

Feix

et al. 2003

Journal of Biological Chemistry

112

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“…The line broadening caused by 5-DOXYL-stearic acid was most pronounced for the detergent resonances of "C atoms located near the polar head-groups, whereas the effect of 16-DOXYL-stearic acid was the largest at the apolar end of the carbon chain (data not shown). Similar results have been obtained for other micellar systems (Brown et al, 1981 ;Mendz et al, 1988Mendz et al, , 1991Papavoine et al, 1994). These results indicate qualitatively that the nitroxide moiety of 16-DOXYL-stearic acid is most of the time near the center of the micelles, whereas the label of 5-DOXYLstearic acid is, on average, close to the surface, i.e.…”

Section: Spin-labeled Probes Incorporated In Micellessupporting

confidence: 87%

“…Using the same spin-label approach the polypeptide-hormone glucagon and the bee-venom constituent melittin were found to bind to the surface of DodPCho micelles (Brown et al, 1981(Brown et al, , 1982. Studies of the myelin basic protein indicated that this molecule is also located primarily near the surface of DodPCho and of mixed DodPCho/palmitoyl/phosphatidic acid micelles (Mendz et al, 1984(Mendz et al, , 1988(Mendz et al, , 1990(Mendz et al, , 1991. A different situation was encountered for the major coat protein of bacteriophage MI 3 ; this protein is composed of a long hydrophobic helix that traverses the SDS micelle and a shorter amphipathic helix that is situated on the surface of the micelle (Papavoine et al, 1994).…”

Section: Spin-labeled Probes Incorporated In Micellesmentioning

confidence: 99%

Surface Location and Orientation of the Lantibiotic Nisin Bound to Membrane‐Mimicking Micelles of Dodecylphosphocholine and of Sodium Dodecylsulphate

Hooven

Spronk

Kamp

et al. 1996

European Journal of Biochemistry

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The interaction of nisin, a membrane-interacting cationic polypeptide, with membranemimicking micelles of zwitterionic dodecylphosphocholine and of anionic sodium dodecylsulphate was studied. Direct contacts have been established through the observation of NOES between nisin and micelle protons. Spin-labeled DOXYL-stearic acids were incorporated into the two micellar systems. From the paramagnetic broadening effects induced in the 'H-NMR spectrum of nisin it is concluded that the molecule is localized at the surface of the micelles. Biochem. 235,. The hydrophobic residues are immersed into the micelles and oriented towards the center, whereas the more polar or charged residues have an outward orientation. The micellar systems are considered to model the first step in the mechanism of antimicrobial action of nisin, this step is the binding of nisin to the cytoplasmic membrane of target bacteria. Detailed information on this initial binding step is obtained. Hydrophobic and electrostatic interactions appear to be involved in the nisin-micelle contacts. It is suggested that subtilin, a lantibiotic structurally related to nisin, has a comparable membrane interaction surface.Keywords: bacteriocin; lanthionine-containing polypeptide; inode of action; NMR; spin labelThe polycyclic 34-residue-containing polypeptide nisin (Gross and Morel], 1971) ( Fig. 1) belongs to the class of lanthionine-containing polypeptides known as lantibiotics (Schnell et al., 1988). They are characterized by the occurrence of unusual amino acids, such as lanthionine, 3methyllanthionine, dehydroalanine (Dha) and dehydrobutyrine (Dhb). Lantibiotics are the end products of ribosomal synthesis and post-translational modifications. They are produced by a large number of Grampositive bacteria; the producer of nisin is Lactococcus lactis subsp. lactis. The post-translational modification involves dehydration of serines and threonines resulting in cx,p-unsaturated amino acids, of which some react with thiol groups of cysteine residues to form lanthionine or 3-methyllanthionine (Ingram, 1970).Nisin possesses bactericidal activity against a wide range of Gram-positive bacteria or their spores. Because of this activity it is exploited as a food preservative in the dairy and canning Correspondence fo C. W. Hilbers, NSR Center, Faculty of Science, Laboratory of Biophysical Chemistry, Toernooiveld, NL-6525 ED Nijmegen, The Netherlands Fux: +31 24 3652112. Ahhvevicztions. Ah:, 3-methylalanyl moiety of (2S, 3S, 6X)-3-metliyllanthionine; Ah,, i,-alanyl moiety of tnesn-lanthionine; .Ah, L-alanyl moicty of meso-lanthioninc or of (2S, 3S, hR)-3-methyllanthionine; 1/2/

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“…Lyso-PC increases the expression of various growth factors and adhesive molecules in endothelial cells (28 -31), and it was shown recently that lysophosphatidylcholine can modulate gene expression independently of PKC and MAPK (31,79,80). In our study, lyso-PC was the only lysolipid tested that stimulates arachidonate release, despite the fact that other lysolipids also possess detergent properties (81,82). Furthermore, the stimulation of arachidonate release by lyso-PC parallels earlier observations that the ability of lyso-PC to stimulate PKC is unique among lysolipids (50,51).…”

Section: Lyso-pc-induced Arachidonate Release In Endothelial Cellsmentioning

confidence: 50%

Lysophosphatidylcholine Stimulates the Release of Arachidonic Acid in Human Endothelial Cells

Wong¹,

Tran²,

Pierce³

et al. 1998

Journal of Biological Chemistry

106

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Lysophosphatidylcholine (lyso-PC) is a product of phosphatidylcholine hydrolysis by phospholipase A 2 (PLA 2 ) and is present in cell membranes, oxidized lipoproteins, and atherosclerotic tissues. It has the ability to alter endothelial functions and is regarded as a causal agent in atherogenesis. In this study, the modulation of arachidonate release by lyso-PC in human umbilical vein endothelial cells was examined. Incubation of endothelial cells with lyso-PC resulted in an enhanced release of arachidonate in a time-and concentration-dependent manner. Maximum arachidonate release was observed at 10 min of incubation with 50 M lyso-PC. Lyso-PC species containing palmitoyl (C 16:0 ) or stearoyl (C 18:0 ) groups elicited the enhancement of arachidonate release, while other lysolipids such as lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol, or lysophosphatidate were relatively ineffective. Lyso-PC-induced arachidonate release was decreased by treatment of cells with PLA 2 inhibitors such as para-bromophenacyl bromide and arachidonoyl trifluoromethyl ketone. Furthermore, arachidonate release was attenuated in cells grown in the presence of antisense oligodeoxynucleotides that specifically bind cytosolic PLA 2 mRNA. Treatment of cells with lyso-PC resulted in a translocation of PLA 2 activity from the cytosolic to the membrane fractions of cells. Lyso-PC induced a rapid influx of Ca 2؉ from the medium into the cells, with a simultaneous enhancement of protein kinase C (PKC) activity in the membrane fractions. The lyso-PC-induced arachidonate release was attenuated when cells were preincubated with specific inhibitors of PKC (staurosporine and Ro31-8220) or a specific inhibitor of mitogen-activated protein kinase/extracellular regulated kinase kinase (PD098059). Taken together, the results of this study show that lyso-PC caused the elevation of cellular Ca 2؉ and the activation of PKC, which stimulated cytosolic PLA 2 in an indirect manner and resulted in an enhanced release of arachidonate.

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Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles

Cited by 35 publications

References 38 publications

Membrane-anchoring and Charge Effects in the Interaction of Myelin Basic Protein with Lipid Bilayers Studied by Site-directed Spin Labeling

Membrane-anchoring and Charge Effects in the Interaction of Myelin Basic Protein with Lipid Bilayers Studied by Site-directed Spin Labeling

Surface Location and Orientation of the Lantibiotic Nisin Bound to Membrane‐Mimicking Micelles of Dodecylphosphocholine and of Sodium Dodecylsulphate

Lysophosphatidylcholine Stimulates the Release of Arachidonic Acid in Human Endothelial Cells

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