The Parkinson's Disease-Associated H50Q Mutation Accelerates α-Synuclein Aggregation in Vitro

被引：152

作者：

Ghosh, Dhiman ^{[1
]}

Mondal, Mrityunjoy ^{[1
]}

Mohite, Ganesh M. ^{[1
]}

Singh, Pradeep K. ^{[1
]}

Ranjan, Priyatosh ^{[1
]}

Anoop, A. ^{[1
]}

Ghosh, Saikat ^{[1
]}

Jha, Narendra Nath ^{[1
]}

Kumar, Ashutosh ^{[1
]}

Maji, Samir K. ^{[1
]}

机构：

[1] Indian Inst Technol, Dept Biosci & Bioengn, Bombay 400076, Maharashtra, India

来源：

BIOCHEMISTRY | 2013年 / 52卷 / 40期

关键词：

FREE-ENERGY LANDSCAPES; WILD-TYPE; PROTEIN; DYNAMICS; IMPACT;

D O I：

10.1021/bi400999d

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

alpha-Synuclein (alpha-Syn) aggregation is directly linked with Parkinson's disease (PD) pathogenesis. Here, we analyzed the aggregation of newly discovered a-Syn missense mutant H50Q in vitro and found that this mutation significantly accelerates the aggregation and amyloid formation of alpha-Syn. This mutation, however, did not alter the overall secondary structure as suggested by two-dimensional nuclear magnetic resonance and circular dichroism spectroscopy. The initial oligomerization study by cross-linking and chromatographic techniques suggested that this mutant oligomerizes to an extent similar to that of the wild-type alpha-Syn protein. Understanding the aggregation mechanism of this H50Q mutant may help to establish the aggregation and phenotypic relationship of this novel mutant in PD.

引用

页码：6925 / 6927

页数：3

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