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Dioleoyl‐phosphatidic acid selectively binds to α‐synuclein and strongly induces its aggregation
Author(s) -
Mizuno Satoru,
Sasai Hirotaka,
Kume Aiko,
Takahashi Daisuke,
Satoh Mamoru,
Kado Sayaka,
Sakane Fumio
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12592
Subject(s) - phosphatidic acid , chemistry , random coil , biophysics , biochemistry , protein aggregation , stereochemistry , protein secondary structure , biology , phospholipid , membrane
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.