Interactions of Synphilin‐1 with phospholipids and lipid membranes
Interactions of Synphilin‐1 with phospholipids and lipid membranes
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DOI：
10.1016/j.febslet.2006.07.019
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发表时间：
2006-08
期刊：
影响因子：
3.5
通讯作者：
Tetsuya Takahashi;H. Yamashita;Y. Nagano;Takeshi Nakamura;T. Kohriyama;M. Matsumoto
中科院分区：
文献类型：
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作者：
Tetsuya Takahashi;H. Yamashita;Y. Nagano;Takeshi Nakamura;T. Kohriyama;M. Matsumoto
SynPhilin-1是一种α-突触核蛋白结合蛋白，参与了帕金森病的发病机制。本研究考察了SynPhilin-1的磷脂结合能力，发现SynPhilin-1的C末端选择性地与酸性磷脂结合，包括磷脂酸、磷脂酰丝氨酸和磷脂酰甘油，但不与自然带电的磷脂结合。SynPhilin-1定位于哺乳动物细胞内的细胞质脂滴。氨基酸序列610-640代表磷脂结合的主要决定位点。此外，在帕金森氏病中发现的R621C突变消除了SynPhilin-1与脂滴的关联。SynPhilin-1的亲脂性可能与其生理功能有关。
Synphilin‐1 is an α‐synuclein binding protein that is involved in the pathogenesis of Parkinson's disease. The present study investigated the phospholipid‐binding capacity of Synphilin‐1. The C‐terminus of Synphilin‐1 was found to selectively bind to acidic phospholipids, including phosphatidic acid, phosphatidylserine, and phosphatidylglycerol, but not to naturally charged phospholipids. Synphilin‐1 was targeted to cytoplasmic lipid droplets in mammalian cells. The amino acid sequence 610–640 was found to represent the primary determinant site for phospholipid binding. Moreover, the R621C mutation identified in Parkinson's disease abolished Synphilin‐1 association with lipid droplets. The lipophilicity of Synphilin‐1 might prove relevant to its physiologic function.