title: Dioleoyl-phosphatidic acid selectively binds to α-synuclein and strongly induces its aggregation.
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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sasai
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kume
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahashi
authors.affiliation: Division of Clinical Mass Spectrometry, Chiba University Hospital, Japan.|Center for Analytical Instrumentation, Chiba University, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Center for Analytical Instrumentation, Chiba University, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kado
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakane
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D019286:Endopeptidase K / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010712:Phosphatidic Acids / Q000737:chemistry*; D066329:Protein Aggregates; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D059748:Proteolysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D008081:Liposomes; D010712:Phosphatidic Acids; D066329:Protein Aggregates; D011994:Recombinant Proteins; D051844:alpha-Synuclein; C037657:dioleoylphosphatidic acid; D019286:Endopeptidase K
keywords: Parkinson's disease; aggregation; phosphatidic acid; α-helix; α-synuclein