Bis(monoacylglycero)phosphate Forms Stable Small Lamellar Vesicle Structures: Insights into Vesicular Body Formation in Endosomes

Bis(monoacylglycero)phosphate Forms Stable Small Lamellar Vesicle Structures: Insights into Vesicular Body Formation in Endosomes
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DOI:
10.1016/j.bpj.2008.12.3892
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发表时间:
2009-03-04
影响因子:
3.4
通讯作者:
Fanucci, Gail E.
Fanucci, Gail E.
中科院分区:
生物学3区
文献类型:
--
作者:
Frederick, Thomas E.;Chebukati, Janetricks N.;Fanucci, Gail E.

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双(单酰基甘油)磷酸(BMP)是一种形状异常的脂质,在晚期核内体中的比例相对较高。在这里,我们报告的动态光散射,透射电子显微镜,核磁共振(NMR)光谱和电子顺磁共振光谱的形态和分子组织的二油酰-BMP(DOBMP)的表征。水合DOBMP分散体的形态随pH和离子强度而变化,并且DOBMP囊泡的直径显著小于磷脂酰胆碱分散体。在中性pH下,DOBMP形成高度结构化的、尺寸为500 nm的簇状分散体。另一方面,在酸性pH下,形成球形囊泡。核磁共振和自旋标记电子顺磁共振表明,DOBMP形成一个层状中间相与酰基链包装类似的其他不饱和磷脂。P-31 NMR揭示了DOBMP中磷酸基团的取向与其他磷脂的取向显著不同。这些宏观和微观结构表征表明,BMP在成熟内体的内腔膜上的生物合成可能产生高BMP含量的出芽囊泡,其形成由BMP脂质的物理性质稳定的小囊泡结构。
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. P-31 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.