Department of Biointerface Chemistry, Faculty of Pharmaceutical Sciences, University of Toyama.
Chem Pharm Bull (Tokyo). 2022;70(8):519-523. doi: 10.1248/cpb.c22-00133.
Lipid transbilayer movement (flip-flop) is regulated by membrane proteins that are involved in homeostasis and signaling in eukaryotic cells. In the plasma membrane, an asymmetric lipid composition is maintained by energy-dependent unidirectional transport. Energy-independent flip-flop promotion by phospholipid scramblases disrupts the asymmetry in several physiological processes, such as apoptosis and blood coagulation. In the endoplasmic reticulum, rapid flip-flop is essential for bilayer integrity because phospholipids are synthesized only in the cytoplasmic leaflet. Phospholipid scramblases are also involved in lipoprotein biogenesis, autophagosome formation, and viral infection. Although several scramblases have been identified and investigated, the precise flip-flop promotion mechanisms are not fully understood. Model transmembrane peptides are valuable tools for investigating the general effects of lipid-peptide interactions. We focus on the development of model transmembrane peptides with flip-flop promotion abilities and their mechanisms.
脂双层跨膜运动（翻转）受参与真核细胞内稳态和信号转导的膜蛋白调节。在质膜中，通过能量依赖的单向转运来维持不对称的脂质组成。磷脂翻转酶的能量非依赖性翻转促进作用会破坏几种生理过程的不对称性，如细胞凋亡和血液凝固。在内质网中，快速翻转对于双层完整性至关重要，因为磷脂仅在细胞质小叶中合成。磷脂翻转酶还参与脂蛋白生物发生、自噬体形成和病毒感染。尽管已经鉴定和研究了几种翻转酶，但翻转促进机制尚不完全清楚。模型跨膜肽是研究脂质-肽相互作用一般影响的有价值工具。我们专注于具有翻转促进能力的模型跨膜肽及其机制的开发。
