Conformational properties of α-synuclein in its free and lipid-associated states

被引:885
作者
Eliezer, D [1 ]
Kutluay, E
Bussell, R
Browne, G
机构
[1] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Program Struct Biol, New York, NY 10021 USA
关键词
alpha-synuclein; protein folding; protein aggregation; membrane binding; Parkinson's disease;
D O I
10.1006/jmbi.2001.4538
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
alpha -Synuclein (alphaS) is a presynaptic terminal protein that is believed to play an important role in the pathogenesis of Parkinson's disease (PD). We have used NMR spectroscopy to characterize the conformational properties of alphaS in solution as a free monomer and when bound to lipid vesicles and lipid-mimetic detergent micelles. Free wild-type alphaS is largely unfolded in solution, but exhibits a region with a preference for helical conformations that may be important in the aggregation of alphaS into fibrils. The N-terminal region of alphaS binds to synthetic lipid vesicles and deter gent micelles in vitro and adopts a highly helical conformation, consistent with predictions based on sequence analysis. The C-terminal part of the protein does not associate with either vesicles or micelles, remaining free and unfolded. These results suggest that one function of alphaS may be to tether as of yet unidentified partners to lipid surfaces via interactions with its C-terminal tail. (C) 2001 Academic Press.
引用
收藏
页码:1061 / 1073
页数:13
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