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首页> 外文期刊>The European Journal of Neuroscience >Parkin occurs in a stable, non-covalent, approximately 110-kDa complex in brain.
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Parkin occurs in a stable, non-covalent, approximately 110-kDa complex in brain.

机译：帕金菌以稳定的，非共价的，约110kDa的复合物存在于大脑中。

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摘要

Mutations in the gene for parkin, a 52-kDa E3 ubiquitin ligase, are a major cause of hereditary Parkinson's disease (PD). In vitro studies have identified a large number of parkin-interacting proteins. Whether parkin exists as a monomer or as part of a stable protein complex in vivo is uncertain. Here we demonstrate that endogenous parkin occurs in a stable, non-covalent, approximately 110-kDa complex in native extracts from mouse brain, heart and skeletal muscle, while monomeric parkin is undetectable. Partial denaturation experiments indicate that this complex is at least a tetramer. Reported parkin-binding partners do not show detectable association with the parkin complex on native gels. Upon overexpression in COS1, SH-SY5Y or CHO cells, parkin accumulates predominantly as a monomer, suggesting that the interactors required for complex formation are available in limiting amounts in these cells. Importantly, PD-linked parkin mutations significantly impair parkin complex formation. These data demonstrate that parkin oligomerizes into a stable, non-covalent, heteromeric complex in vivo, and suggest that parkin may have as yet unidentified stable binding partners.
机译：帕金基因（一种52 kDa E3泛素连接酶）的基因突变是遗传性帕金森氏病（PD）的主要原因。体外研究已鉴定出大量与帕金蛋白相互作用的蛋白。帕金蛋白在体内是否以单体形式存在或作为稳定蛋白复合物的一部分存在不确定性。在这里，我们证明内源性帕金蛋白以稳定，非共价，约110 kDa的复合物形式存在于小鼠大脑，心脏和骨骼肌的天然提取物中，而单体帕金蛋白则不可检测。部分变性实验表明该络合物至少是四聚体。据报道，与Parkin结合的伴侣在天然凝胶上未显示与Parkin复合物的可检测关联。在COS1，SH-SY5Y或CHO细胞中过表达后，派克蛋白主要以单体形式积累，这表明在这些细胞中，形成复合物所需的相互作用物数量有限。重要的是，PD连锁的帕金突变显着削弱了帕金复合物的形成。这些数据表明，帕金蛋白在体内低聚为稳定的，非共价的异聚复合物，并表明帕金蛋白可能具有尚未确定的稳定结合伴侣。

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