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首页> 外文期刊>Journal of pharmaceutical sciences. >Structural stability of vault particles.
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Structural stability of vault particles.

机译：穹顶颗粒的结构稳定性。

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摘要

Vaults, at 13 MDa, are the largest ribonucleoprotein particles known. In vitro, expression of the major vault protein (MVP) alone in Sf9 insect cells results in the production of recombinant particles with characteristic vault structure. With the ultimate goal of using recombinant vaults as nanocapsules for the delivery of biomolecules, we have employed a variety of spectroscopic techniques (i.e., circular dichroism, fluorescence spectroscopy, and light scattering) along with electron microscopy, to characterize the structural stability of vaults over a wide range of pH (3-8) and temperature (10-90 degrees C). Ten different conformational states of the vaults were identified over the pH and temperature range studied with the most stable region at pH 6-8 below 40 degrees C and least stable at pH 4-6 above 60 degrees C. A unique intermediate molten globulelike state was also identified at pH 6 and approximately 55 degrees C. EM imaging showed the opening of intact vaults into flowerlike structures when transitioning from neutral to acidic pH. This information has potential use in the development of recombinant vaults into nanocapsules for drug delivery since one mechanism by which therapeutic agents entrapped in vaults could be released is through an opening of the intact vault structure.
机译：保育库为13 MDa，是已知的最大核糖核蛋白颗粒。在体外，仅在Sf9昆虫细胞中表达主要穹顶蛋白（MVP）导致产生具有特征穹顶结构的重组颗粒。为了将重组保管库作为纳米胶囊用于生物分子的传递，我们采用了多种光谱技术（例如，圆二色性，荧光光谱和光散射）以及电子显微镜技术来表征保管库的结构稳定性。 pH（3-8）和温度（10-90摄氏度）的范围很广。在所研究的pH和温度范围内，确定了穹顶的十种不同构象状态，其中在40摄氏度以下的pH 6-8处于最稳定的区域，在60摄氏度以上的pH 4-6处于最不稳定的区域。在pH为6和约55℃时也可鉴定出。EM成像显示当从中性pH过渡至酸性pH时，完整的穹into打开成花状结构。该信息在将重组穹顶发展为用于药物递送的纳米胶囊中具有潜在的用途，因为可以释放完整的穹顶结构来释放被包裹在穹顶中的治疗剂的一种机制。

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