Dioleoyl‐phosphatidic acid selectively binds to α‐synuclein and strongly induces its aggregation. Issue 5 (23rd February 2017)

• Record Type: Journal Article
• Authors: Mizuno, Satoru; Sasai, Hirotaka; Kume, Aiko; Takahashi, Daisuke; Satoh, Mamoru; Kado, Sayaka; Sakane, Fumio
• Is Part Of: FEBS letters. Volume 591:Issue 5(2017)
• Page Start: 784
• Page End: 791
• Publication Date: 2017-02-23
• Subjects: aggregation -- Parkinson's disease -- phosphatidic acid -- α‐helix -- α‐synuclein; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12592
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract :