Semisynthetic, Site-Specific Ubiquitin Modification of α-Synuclein Reveals Differential Effects on Aggregation

被引：92

作者：

Meier, Franziska ^{[1
]}

Abeywardana, Tharindumala ^{[1
]}

Dhall, Abhinav ^{[5
]}

Marotta, Nicholas P. ^{[1
]}

Varkey, Jobin ^{[3
,4
]}

Langen, Ralf ^{[3
,4
]}

Chatterjee, Champak ^{[5
]}

Pratt, Matthew R. ^{[1
,2
]}

机构：

[1] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA

[2] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA

[3] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Zilka Neurogenet Inst, Los Angeles, CA 90089 USA

[5] Univ Washington, Dept Chem, Seattle, WA 98195 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2012年 / 134卷 / 12期

基金：

美国国家卫生研究院;

关键词：

PARKINSONS-DISEASE; PATHOGENESIS; FIBRILLATION; FIBRILS; PHOSPHORYLATION; OLIGOMERS; PROMOTES; CELLS; NMR;

D O I：

10.1021/ja300094r

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The process of neurodegeneration in Parkinson's Disease is intimately associated with the aggregation of the protein a-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 a-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 alpha-synuclein derivatives and have demonstrated that different ubiquitination sites have differential effects on alpha-synuclein aggregation.

引用

页码：5468 / 5471

页数：4

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