Dioleoyl-phosphatidic acid selectively binds to a-synuclein and strongly induces its aggregation

被引：34

作者：

Mizuno, Satoru ^{[1
]}

Sasai, Hirotaka ^{[1
]}

Kume, Aiko ^{[1
]}

Takahashi, Daisuke ^{[1
]}

Satoh, Mamoru ^{[2
,3
]}

Kado, Sayaka ^{[3
]}

Sakane, Fumio ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Sci, Dept Chem, Chiba, Japan

[2] Chiba Univ Hosp, Div Clin Mass Spectrometry, Chiba, Japan

[3] Chiba Univ, Ctr Analyt Instrumentat, Chiba, Japan

来源：

FEBS LETTERS | 2017年 / 591卷 / 05期

基金：

日本科学技术振兴机构;

关键词：

aggregation; Parkinson's disease; phosphatidic acid; a-helix; a-synuclein; PROTEIN SECONDARY STRUCTURE; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; DIACYLGLYCEROL KINASES; MEMBRANE; RISK; BRAIN; PHOSPHOLIPIDS; ASSOCIATION; ACTIVATION;

D O I：

10.1002/1873-3468.12592

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 (alpha-syn), which causally links to Parkinson's disease, binds to vesicles containing phosphatidic acid (PA). However, the effects of the fatty acyl chains of PA on its ability to bind to alpha-syn protein remain unclear. Intriguingly, we reveal that among several PA species, 18:1/18:1-PA is the most strongly bound PA to the alpha-syn protein. Moreover, 18:1/18:1-PA more strongly enhances secondary structural changes from the random coil form to the alpha-helical form than 16:0/18:1-PA. Furthermore, 18:1/18:1-PA more markedly accelerates generation of multimeric and proteinase K-resistant alpha-syn protein compared to 16:0/ 18:1-PA. These results indicate that among phospholipids examined so far, 18:1/18:1-PA demonstrates the strongest binding to alpha-syn, as well as the most effective enhancement of its secondary structural changes and aggregation formation.

引用

页码：784 / 791

页数：8

共 42 条

[11] THE PRECURSOR PROTEIN OF NON-A-BETA COMPONENT OF ALZHEIMERS-DISEASE AMYLOID IS A PRESYNAPTIC PROTEIN OF THE CENTRAL-NERVOUS-SYSTEM [J].