Bis(monoacylglycero)phosphate Forms Stable Small Lamellar Vesicle Structures: Insights into Vesicular Body Formation in Endosomes |
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Authors: | Thomas E. Frederick |
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Affiliation: | Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200 |
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Abstract: | Bis(monoacylglycero)phosphate (BMP) is an unusually shaped lipid found in relatively high percentage in the late endosome. Here, we report the characterization of the morphology and molecular organization of dioleoyl-BMP (DOBMP) with dynamic light scattering, transmission electron microscopy, nuclear magnetic resonance (NMR) spectroscopy, and electron paramagnetic resonance spectroscopy. The morphology of hydrated DOBMP dispersions varies with pH and ionic strength, and DOBMP vesicles are significantly smaller in diameter than phosphatidylcholine dispersions. At neutral pH, DOBMP forms highly structured, clustered dispersions 500 nm in size. On the other hand, at acidic pH, spherically shaped vesicles are formed. NMR and spin-labeled electron paramagnetic resonance demonstrate that DOBMP forms a lamellar mesophase with acyl-chain packing similar to that of other unsaturated phospholipids. 31P NMR reveals an orientation of the phosphate group in DOBMP that differs significantly from that of other phospholipids. These macroscopic and microscopic structural characterizations suggest that the biosynthesis of BMP on the inner luminal membrane of maturing endosomes may possibly produce budded vesicles high in BMP content, which form small vesicular structures stabilized by the physical properties of the BMP lipid. |
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Keywords: | BMP, bis(monoacylglycero)phosphate BMP18:1, (S,R  isomer)-sn-(3-oleoyl-2-hydroxy)-glycero-1-phospho-sn-3&prime -(1&prime -oleoyl-2&prime -hydroxy)-glycerol POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine EPR, electron paramagnetic resonance LUV, large unilamellar vesicles MLV, multilamellar vesicle VB, vesicular body DLS, dynamic light scattering TLC, thin-layer chromatography TEM, transmission electron microscopy DMBMP, dimyristoyl-BMP DOBMP, dioleoyl-BMP DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine DOPG, 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] POPG, 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] SDS, sodium dodecyl sulfate ANTS, 8-amino-napthalene-1,3,6 trisulfonic acid DPX, p-xylene-bis-pyridinium bromide |
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