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首页> 外文期刊>Journal of Molecular Biology >Physical chemistry of polyglutamine: Intriguing tales of a monotonous sequence
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Physical chemistry of polyglutamine: Intriguing tales of a monotonous sequence

机译：聚谷氨酰胺的物理化学：单调序列的有趣故事

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摘要

Polyglutamine (polyQ) sequences of unknown normal function are present in a significant number of proteins, and their repeat expansion is associated with a number of genetic neurodegenerative diseases. PolyQ solution structure and properties are important not only because of the normal and abnormal biology associated with these sequences but also because they represent an interesting case of a biologically relevant homopolymer. As the common thread in expanded polyQ repeat diseases, it is important to understand the structure and properties of simple polyQ sequences. At the same time, experience has shown that sequences attached to polyQ, whether in artificial constructs or in disease proteins, can influence structure and properties. The two major contenders for the molecular source of the neurotoxicity implicit in polyQ expansion within disease proteins are a populated toxic conformation in the monomer ensemble and a toxic aggregated species. This review summarizes experimental and computational studies on the solution structure and aggregation properties of both simple and complex polyQ sequences, and their repeat-length dependence. As a representative of complex polyQ proteins, the behavior of huntingtin N-terminal fragments, such as exon-1, receives special attention.
机译：正常功能未知的聚谷氨酰胺（polyQ）序列存在于大量蛋白质中，它们的重复扩增与多种遗传性神经退行性疾病有关。 PolyQ溶液的结构和性质很重要，不仅因为与这些序列相关的正常和异常生物学，而且因为它们代表了生物学相关均聚物的有趣案例。作为扩展polyQ重复疾病的共同点，重要的是了解简单polyQ序列的结构和性质。同时，经验表明，无论是在人工构建体中还是在疾病蛋白质中，与polyQ相连的序列都可以影响结构和特性。疾病蛋白内polyQ扩展所隐含的神经毒性的分子来源的两个主要竞争者是单体集合中的填充毒性构象和毒性聚集物种。这篇综述总结了关于简单和复杂polyQ序列的解结构和聚集特性及其重复长度依赖性的实验和计算研究。作为复杂的polyQ蛋白的代表，亨廷顿蛋白N末端片段（例如外显子1）的行为受到特别关注。

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