Extent of Inhibition of α-Synuclein Aggregation in Vitro by SUMOylation Is Conjugation Site- and SUMO Isoform-Selective
Extent of Inhibition of α-Synuclein Aggregation in Vitro by SUMOylation Is Conjugation Site- and SUMO Isoform-Selective
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DOI：
10.1021/bi501512m
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发表时间：
2015-02-03
期刊：
影响因子：
2.9
通讯作者：
Pratt, Matthew R.
中科院分区：
文献类型：
--
作者：
Abeywardana, Tharindumala;Pratt, Matthew R.
α-突触核蛋白是帕金森病中的主要聚集蛋白，可以被小蛋白SUMO修饰，表明在疾病中的潜在作用。然而，由于先前研究的蛋白质的异质性，SUMO化对α-突触核蛋白聚集的影响仍然存在争议。在这里，我们使用蛋白质半合成获得均匀SUMO化的α-突触核蛋白，并发现SUMO化对α-突触核蛋白聚集的位点和亚型依赖性作用。我们的研究结果表明，在K102 SUMO化是一个更好的抑制剂的聚集比相应的修饰在K96和SUMO 1修饰，一个更好的抑制剂比SUMO 3。
alpha-Synuclein, the major aggregating protein in Parkinson's disease, can be modified by the small protein SUMO, indicating a potential role in disease. However, the effects of SUMOylation on alpha-synuclein aggregation remain controversial due to heterogeneous nature of the proteins previously investigated. Here we used protein semisynthesis to obtain homogeneously SUMOylated alpha-synuclein and discovered site- and isoform-dependent effects of SUMOylation on alpha-synuclein aggregation. Our results indicate that SUMOylation at K102 is a better inhibitor of aggregation than corresponding modification at K96 and SUMO1 modification, a better inhibitor than SUMO3.