Mapping long-range interactions in α-synuclein using spin-label NMR and ensemble molecular dynamics simulations

被引：601

作者：

Dedmon, MM ^{[1
]}

Lindorff-Larsen, K ^{[1
]}

Christodoulou, J ^{[1
]}

Vendruscolo, M ^{[1
]}

Dobson, CM ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2005年 / 127卷 / 02期

关键词：

D O I：

10.1021/ja044834j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The intrinsically disordered protein α-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of α-synuclein consists of a broad distribution of conformers with an ensemble-averaged hydrodynamic radius significantly smaller than that expected for a random coil structure. This partial condensation is driven by interactions between the highly charged C-terminus and a large hydrophobic central region of the protein sequence. We suggest that this structure could inhibit the formation of α-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD. Copyright © 2005 American Chemical Society.

引用

页码：476 / 477

页数：2

共 22 条

[1] Cellular polyamines promote the aggregation of α-synuclein [J].