Domain architecture of the polyglutamine protein ataxin-3: a globular domain followed by a flexible tail
Domain architecture of the polyglutamine protein ataxin-3: a globular domain followed by a flexible tail
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DOI：
10.1016/s0014-5793(03)00748-8
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发表时间：
2003-08-14
期刊：
影响因子：
3.5
通讯作者：
Pastore, A
中科院分区：
文献类型：
--
作者：
Masino, L;Musi, V;Pastore, A
蛋白ataxin-3中的聚谷氨酰胺（polyQ）束异常扩张导致脊髓小脑性共济失调3型，这是一种常染色体显性神经退行性疾病。我们对ataxin-3的结构和功能知之甚少，尽管这些信息无疑有助于理解为什么扩增的蛋白形成不溶性核聚集体并导致神经元细胞死亡。为了建立ataxin-3的结构域结构和多q通道在蛋白质环境中的作用，我们使用了一系列技术，从有限的蛋白质水解到圆二色性（CD）和核磁共振（NMR）光谱，研究了人类和小鼠的同源物。这两个蛋白序列共享一个高度保守的n端，不同的只是谷氨酰胺重复序列的长度和c端。我们的数据最终表明，ataxin-3是由一个结构化的n端结构域和一个灵活的尾部组成的。此外，[N-15]谷氨酰胺选择性标记的样品使我们能够通过核磁共振直接了解polyQ区域的结构。(C) 2003年由Elsevier B.V.代表欧洲生化学会联合会出版。
Anomalous expansion of a polyglutamine (polyQ) tract in the protein ataxin-3 causes spinocerebellar ataxia type 3, an autosomal dominant neurodegenerative disease. Very little is known about the structure and the function of ataxin-3, although this information would undoubtedly help to understand why the expanded protein forms insoluble nuclear aggregates and causes neuronal cell death. With the aim of establishing the domain architecture of ataxin-3 and the role of the polyQ tract within the protein context, we have studied the human and murine orthologues using a combination of techniques, which range from limited proteolysis to circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The two protein sequences share a highly conserved N-terminus and differ only in the length of the glutamine repeats and in the C-terminus. Our data conclusively indicate that ataxin-3 is composed by a structured N-terminal domain, followed by a flexible tail. Moreover, [N-15]glutamine selectively labelled samples allowed us to have a direct insight by NMR into the structure of the polyQ region. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.