Self-assembly and gelation of oxidized glutathione in organic solvents
Self-assembly and gelation of oxidized glutathione in organic solvents
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DOI：
10.1021/ja0040417
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发表时间：
2001-05-16
影响因子：
15
通讯作者：
Atkins, WM
中科院分区：
文献类型：
--
作者：
Lyon, RP;Atkins, WM
普遍存在的三肽谷胱甘肽（γ-glu-cys-gly）（GSSG）的氧化二硫化物形式显示在二甲基亚砜水溶液中产生透明的热可逆凝胶。二甲基甲酰胺和甲醇，在GSSG浓度低至1.5 mM。凝胶结合刚果红，并表现出显着的绿色双折射，当观察到之间的交叉偏振片，淀粉样蛋白结构的特征。通过透射电子显微镜，凝胶似乎由直径约75 nm的纤维结构网络组成。几种结构上相关的肽，包括谷胱甘肽异构体glu-cys-gly和谷胱甘肽的乙酰基类似物（β-asp-cys-gly），在类似条件下不能产生凝胶。这些结果表明，产生凝胶化的相互作用是高度特异性的，并且由γ-glu-cys键引入的不寻常的肽几何形状对凝胶化行为是关键的。1H-1 NMR表明γ-谷氨酰基α-和β-质子的溶剂依赖性扰动，圆二色性揭示了在产生凝胶化的条件下二硫键几何形状的变化。我们提出，在适当的有机溶剂中，GSSG自组装成一个扩展的β-片状结构的网络，能够固定本体溶剂。虽然显然是推测性的，但考虑谷胱甘肽可能的生理后果是有趣的：在异常蛋白质聚集和硫醇-二硫键交换等过程中的自我识别，据信这参与了蛋白质折叠。
The oxidized disulfide form of the ubiquitous tripeptide glutathione (gamma -glu-cys-gly) (GSSG) is shown to produce transparent, thermoreversible gels in aqueous solutions of dimethyl sulfoxide. dimethylformamide. and methanol, at GSSG concentrations as low as 1.5 mM. The gels bind Congo Red and exhibit dramatic green birefringence when observed between crossed polarizers, characteristic of amyloid structures. By transmission electron microscopy, the gels appear to consist of a network of fibrous structures about 75 nm in diameter. Several structurally related peptides, including the glutathione isomer glu-cys-gly and the aspartyl analogue of glutathione (beta -asp-cys-gly), failed to produce gels under similar conditions. These results suggest that the interactions which produce gelation are highly specific and that the unusual peptide geometry introduced by gamma -glu-cys linkage is critical to the gelation behavior. H-1 NMR indicates solvent-dependent perturbation of the gamma -glutamyl alpha- and beta -protons and circular dichroism reveals a shift in the geometry of the disulfide bond under conditions producing gelation. We propose that in appropriate organic solvents, GSSG self-assembles into an extended network of beta -sheetlike structures capable of immobilizing bulk solvent. While obviously speculative, it is interesting to consider possible physiological consequences of glutathione: sell-recognition in such processes as abnormal protein aggregation and the thiol-disulfide exchange which is believed to participate in protein folding.