Phosphatidylethanolamine binding protein

Fig. 12.5. Schematic summary of the eight T. canis proteins containing predicted SXC (NC6) domains. The consensus is shown in the N-terminal domain of PEB-1 (phosphatidylethanolamine-binding protein-1) as xCxDxxxDC(6x)C(11x) RCxxTCxxC. This consensus is faithfully repeated in MUC-1 (mucin-1), MUC-2, MUC-4 and MUC-5, and in all but the C-terminal domain of MUC-3. This domain (and the C-terminal SXC domain of PEB-1) show consensus spacing but some variation in consensus residues. Two additional proteins with quadrupled SXC domains differ in spacing between cysteines-2, -3 and -4, and show more variation in consensus residues. These are VAH-1 (venom allergen homologue) and HUF-001 (homologue of unknown function-001).

Gems, D., Ferguson, C.J., Robertson, B.D., Nieves, R, Page, A.P., Blaxter, M.L. and Maizels, R.M. (1995) An abundant, trarav-spliced mRNA from Toxocara canis infective larvae encodes a 26-kDa protein with homology to phosphatidylethanolamine-binding proteins. Journal of Biological Chemistry 270,18157-18522. 

Knoblich JA (2001) Asymmetric cell division during animal development. Nat Rev Mol Cell Biol 2 11-20 Kroslak T, Koch T, Kahl E, Hollt V (2001) Human phosphatidylethanolamine-binding protein facihtates heterotrimeric G protein-dependent signaling. J Biol Chem 276 39772-39778 Lankford K, Cypher C, Letoumeau P (1990) Nerve growth cone motility. Curr Opin Cell Biol 2 80-85 Law GJ, Northrop AJ, Mason WT (1993) Rab3-peptide stimulates exocytosis from mast cells via a pertussis toxin-sensitive mechanism. FEBS Lett 333 56-60... 

Raf-l kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine binding protein (PEBP) family, a highly conserved group of proteins found in a... 

Vallee, B.S., Tauc, R, Brochon, J.C., Maget-Dana, R., Lelievre, D., Metz-Boutigue, M.H., Bureaud, N., and Schoentgen, F. (2001). Behaviour of bovine phosphatidylethanolamine-binding protein with model membranes. Evidence of affinity for negatively chaiged membranes. Eur. J. Biochem. 268, 5831-5841. 

Several studies have evaluated the effects of oral di(2-ethylhexyl) adipate on various aspects of hepatic lipid metabolism. Feeding di(2-ethylhexyl) adipate (2% of diet) to male Wistar rats for seven days resulted in increased hepatic fatty acid-binding protein as well as in increased microsomal stearoyl-CoA desaturation activity (Kawashima et al., 1983a,b). Feeding the compound at this dose for 14 days resulted in increased levels of hepatic phospholipids and a decline in phosphatidyl-choline phosphatidylethanolamine ratio (Yanagita et al., 1987). Feeding di(2-ethyl-hexyl) adipate (2% of diet) to male NZB mice for five days resulted in induction of fatty acid translocase, fatty acid transporter protein and fatty acid binding protein in the liver (Motojima et al., 1998). 

The peptide-induced inhibition of the intercalation of lipid A into liposomes made from phosphatidylserine (PS) alone or mediated by lipopolysaccharide-binding protein (LBP), was determined by FRET spectroscopy applied as a probe dilution assay (4). First the peptide, then lipid A, followed by LBP (or vice versa) were added to the liposomes, which were labelled with the donor dye NBD-phosphatidylethanolamine (NBD-PE) and acceptor dye Rhodamine-PE. The final concentrations were peptide and lipid 1 pM and LBP 0.1 pM. Intercalation was monitored as the increase of the ratio of the donor intensity Id at 531 nm to that of the acceptor intensity U at 593 nm (FRET signal) with on time. 

Once synthesized several factors influence the particular leaflet of the membrane lipid bilayer where the lipids reside. One is static interactions with intrinsic and extrinsic membrane proteins which, by virtue of their mechanism of biosynthesis, are also asymmetric with respect to the membrane. The interaction of the cytoplasmic protein, spectrin with the erythrocye membrane has been the subject of a number of studies. Coupling of spectrin to the transmembrane proteins, band 3 and glycophorin 3 via ankyrin and protein 4.1, respectively, has been well documented (van Doit et al, 1998). Interaction of spectrin with membrane lipids is still somewhat conjectural but recent studies have characterized such interactions more precisely. O Toole et al. (2000) have used a fluorescine derivative of phosphatidylethanolamine to investigate the binding affinity of specttin to lipid bilayers comprised of phosphatidylcholine or a binary mixture of phosphatidylcholine and phosphatidylserine. They concluded on the basis... 

Lipid transfer peptides and proteins occur in eukaryotic and prokaryotic cells. In vitro they possess the ability to transfer phospholipids between lipid membranes. Plant lipid transfer peptides are unspecific in their substrate selectivity. They bind phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and glycolipids. Some of these peptides have shown antifungal activity in vitro The sequences of lipid transfer proteins and peptides contain 91-95 amino acids, are basic, and have eight cysteine residues forming four disulfide bonds. They do not contain tryptophan residues. About 40% of the sequence adopts a helical structure with helices linked via disulfide bonds. The tertiary structure comprises four a-helices. The three-dimensional structure of a lipid transfer peptide from H. vulgare in complex with palmitate has been solved by NMR. In this structure the fatty acid is caged in a hydrophobic cavity formed by the helices. 

To date the evidence seems to favor the binding of tumor promoter to phospholipid in the cell membrane. Specific binding of [3h]TPA to mouse epidermal particulate matter is susceptible to phospholipases C and A2, less susceptible to protease, and completely resistant to glycosidase (32). Photoaffinity labelling studies with [20-3h]-phorbol 12-p-azidobenzoate 13-benzoate indicates that the irreversible binding of this photolabile phorbol ester to mouse brain membrane is predominantly to the phospholipid (specifically phosphatidylethanolamine and phosphatidylserine) portion rather than to the protein portion (33). 

The exact function of the annexin fold family is at present unclear. All of these proteins appear to show calcium-dependent binding to phosphatidylethanolamine or phosphatidylinositol liposomes. In addition, they can promote fusion of liposomes, and because of this property, it has been suggested that these proteins might mediate calcium dependent exocytosis. P36 and p35 have also been shown to bind to F-actin and spectrin [65,66]. Recently, Khanna et al. [70] have reported a procedure for the simultaneous purification of p35, p36 oligomer and p36 monomer from bovine lung, and identified all three proteins as substrates of protein kinase C. Furthermore, the work of Huang et al. [86] and Khanna et al. [69] has suggested that all three proteins are inhibitors of phospholipase A2. Further experiments will be required to clarify the function of these proteins. 

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