α-突触核蛋白的半合成、定点泛素化修饰揭示了对聚集的差异影响。
Semisynthetic, site-specific ubiquitin modification of α-synuclein reveals differential effects on aggregation.
机构信息
Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
出版信息
J Am Chem Soc. 2012 Mar 28;134(12):5468-71. doi: 10.1021/ja300094r. Epub 2012 Mar 14.
Abstract
The process of neurodegeneration in Parkinson's Disease is intimately associated with the aggregation of the protein α-synuclein into toxic oligomers and fibrils. Interestingly, many of these protein aggregates are found to be post-translationally modified by ubiquitin at several different lysine residues. However, the inability to generate homogeneously ubiquitin modified α-synuclein at each site has prevented the understanding of the specific biochemical consequences. We have used protein semisynthesis to generate nine site-specifically ubiquitin modified α-synuclein derivatives and have demonstrated that different ubiquitination sites have differential effects on α-synuclein aggregation.
摘要
帕金森病中的神经退行性过程与蛋白质α-突触核蛋白聚集成有毒寡聚物和原纤维密切相关。有趣的是，这些蛋白质聚集体中的许多都被泛素在几个不同的赖氨酸残基上进行翻译后修饰。然而，由于无法在每个位点生成均匀的泛素修饰的α-突触核蛋白，因此无法了解特定的生化后果。我们使用蛋白质半合成生成了九个位点特异性泛素修饰的α-突触核蛋白衍生物，并证明了不同的泛素化位点对α-突触核蛋白聚集有不同的影响。
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