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

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

doi:10.1002/1873-3468.12592

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

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

Pharmaceutical Health Care and Sciences

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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.

Original language	English
Pages (from-to)	784-791
Number of pages	8
Journal	FEBS Letters
Volume	591
Issue number	5
DOIs	https://doi.org/10.1002/1873-3468.12592
Publication status	Published - Mar 2017

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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.",

author = "Satoru Mizuno and Hirotaka Sasai and Aiko Kume and Daisuke Takahashi and Mamoru Satoh and Sayaka Kado and Fumio Sakane",

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T1 - Dioleoyl-phosphatidic acid selectively binds to α-synuclein and strongly induces its aggregation

AU - Mizuno, Satoru

AU - Sasai, Hirotaka

AU - Kume, Aiko

AU - Takahashi, Daisuke

AU - Satoh, Mamoru

AU - Kado, Sayaka

AU - Sakane, Fumio

PY - 2017/3

Y1 - 2017/3

N2 - 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.

AB - 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.

U2 - 10.1002/1873-3468.12592

DO - 10.1002/1873-3468.12592

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SN - 0014-5793

VL - 591

SP - 784

EP - 791

JO - FEBS Letters

JF - FEBS Letters

IS - 5

ER -

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

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