...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant
【24h】

Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant

机译：天然渗透保护剂在体外和体内抑制蛋白质聚集

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Small organic molecules termed osmolytes are harnessed by a variety of cell types in a wide range of organisms to counter unfavorable physiological conditions that challenge protein stability and function. Using a well characterized reporter system that we developed to allow in vivo observations, we have explored how the osmolyte proline influences the stability and aggregation of a model aggregation-prone protein, P39A cellular retinoic acid-binding protein. Strikingly, we find that the natural osmolyte proline abrogates aggregation both in vitro and in vivo (in an Escherichia coli expression system). Importantly, proline also prevented aggregation of constructs containing exon 1 of huntingtin with extended polyglutamine tracts. Although compatible osmolytes are known to stabilize the native state, our results point to a destabilizing effect of proline on partially folded states and early aggregates and a solubilizing effect on the native state. Because proline is believed to act through a combination of solvophobic backbone interactions and favorable side-chain interactions that are not specific to a particular sequence or structure, the observed effect is likely to be general. Thus, the osmolyte proline may be protective against biomedically important protein aggregates that are hallmarks of several late-onset neurodegen-erative diseases including Huntington's, Alzheimer's, and Parkinson's. In addition, these results should be of practical importance because they may enable protein expression at higher efficiency under conditions where aggregation competes with proper folding.
机译：广泛的生物体中的各种细胞类型都利用称为渗透压的有机小分子来应对不利的生理条件，这些条件会挑战蛋白质的稳定性和功能。使用我们开发的特性良好的报告系统，可以进行体内观察，我们研究了渗透压脯氨酸如何影响易于发生模型聚集的蛋白P39A细胞视黄酸结合蛋白的稳定性和聚集。令人惊讶地，我们发现天然渗透压脯氨酸在体外和体内（在大肠杆菌表达系统中）都消除了聚集。重要的是，脯氨酸还可以防止含有亨廷顿外显子1的构建体与扩展的聚谷氨酰胺束聚集。尽管已知相容的渗透压可稳定天然状态，但我们的结果表明脯氨酸对部分折叠状态和早期聚集体具有去稳定作用，并对天然状态具有增溶作用。由于脯氨酸被认为是通过疏溶剂性主链相互作用和非特定序列或结构的有利侧链相互作用的组合起作用的，因此观察到的效果可能是普遍的。因此，渗透压脯氨酸可以保护生物医学上重要的蛋白质聚集体，这些聚集体是几种迟发性神经退行性疾病的标志，包括亨廷顿病，阿尔茨海默氏病和帕金森氏病。另外，这些结果应具有实际意义，因为它们可以在聚集与适当折叠竞争的条件下以更高的效率表达蛋白质。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号