Identification of a self-association region within the SCA1 gene product, ataxin-1
Identification of a self-association region within the SCA1 gene product, ataxin-1
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DOI：
10.1093/hmg/6.4.513
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发表时间：
1997-04-01
影响因子：
3.5
通讯作者：
Orr, HT
中科院分区：
文献类型：
--
作者：
Burright, EN;Davidson, JD;Orr, HT
脊髓小脑性共济失调 1 型 (SCA1) 是一种常染色体显性神经退行性疾病，由 SCA I 基因产物 ataxin-1 内的聚谷氨酰胺束扩张引起。据信，该束的扩展可能导致突变蛋白获得功能，可能是通过改变自关联或与其他细胞蛋白的相互作用，我们使用酵母二杂交系统来确定ataxin-1是否能够多聚化，该分析表明，ataxin-1确实具有自关联的能力，然而，这种关联似乎不受多聚谷氨酰胺束的扩展的影响，与此一致 结果发现，缺失分析排除了ataxin-1自缔合中多聚谷氨酰胺束的参与，而是将多聚化区域定位于野生型蛋白的氨基酸495-605。这些结果虽然鉴定了ataxin-1自相互作用区域，但未能支持涉及ataxin-1多聚谷氨酰胺束的极性拉链介导的多聚化模型。
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract within the SCA I gene product, ataxin-1. Expansion of this tract is believed to result in a gain of function by the mutant protein, perhaps through altered self-associations or interactions with other cellular proteins, We have used the yeast two hybrid system to determine if ataxin-1 is capable of multimerization, This analysis revealed that ataxin-1 does have the ability to self-associate, however, this association does not appear to be influenced by expansion of the polyglutamine tract, Consistent with this finding, deletion analysis excluded the involvement of the polyglutamine tract in ataxin-1 self-association, and instead localized the multimerization region to amino acids 495-605 of the wild type protein, These results, while identifying an ataxin-1 self-interaction region, fail to support a proposed model of polar-zipper mediated multimerization involving the ataxin-1 polyglutamine tract.