Mizuno Satoru, Sasai Hirotaka, Kume Aiko, Takahashi Daisuke, Satoh Mamoru, Kado Sayaka, Sakane Fumio
Department of Chemistry, Graduate School of Science, Chiba University, Japan.
Division of Clinical Mass Spectrometry, Chiba University Hospital, Japan.
FEBS Lett. 2017 Mar;591(5):784-791. doi: 10.1002/1873-3468.12592. Epub 2017 Feb 23.
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.
与帕金森病存在因果关联的α-突触核蛋白（α-syn）可与含有磷脂酸（PA）的囊泡结合。然而，PA的脂肪酰链对其与α-syn蛋白结合能力的影响仍不清楚。有趣的是，我们发现，在几种PA种类中，18:1/18:1-PA是与α-syn蛋白结合最紧密的PA。此外，与16:0/18:1-PA相比，18:1/18:1-PA能更强烈地促进α-syn蛋白从无规卷曲形式向α-螺旋形式的二级结构转变。此外，与16:0/18:1-PA相比，18:1/18:1-PA能更显著地加速多聚体和蛋白酶K抗性α-syn蛋白的生成。这些结果表明，在目前所检测的磷脂中，18:1/18:1-PA与α-syn的结合力最强，对其二级结构转变和聚集体形成的促进作用也最有效。
