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

July 28, 2017

Title

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

Author

Satoru Mizuno, Hirotaka Sasai, Aiko Kume, Daisuke Takahashi, Mamoru Satoh, Sayaka Kado, Fumio Sakane

Year

2017

Journal

FEBS Letters

Abstract

α-Synuclein (α-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 α-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 α-syn protein. Moreover, 18:1/18:1-PA more strongly enhances secondary structural changes from the random coil form to the α-helical form than 16:0/18:1-PA. Furthermore, 18:1/18:1-PA more markedly accelerates generation of multimeric and proteinase K-resistant α-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 α-syn, as well as the most effective enhancement of its secondary structural changes and aggregation formation.

Instrument

J-805

Keywords

Circular dichroism, Secondary structure, Vesicle interactions, Biochemistry