Tadini-Buoninsegni Francesco, Mikkelsen Stine A, Mogensen Louise S, Holm Rikke, Molday Robert S, Andersen Jens Peter
Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.
Department of Biomedicine, Aarhus University, Denmark.
FEBS Lett. 2023 Feb;597(4):495-503. doi: 10.1002/1873-3468.14459. Epub 2022 Aug 9.
ATP8A2 is a mammalian P4-ATPase (flippase) that translocates the negatively charged lipid substrate phosphatidylserine from the exoplasmic leaflet to the cytoplasmic leaflet of cellular membranes. Using an electrophysiological method based on solid supported membranes, we investigated the electrogenicity of specific reaction steps of ATP8A2 and explored a potential phospholipid translocation pathway involving residues with positively charged side chains. Changes to the current signals caused by mutations show that the main electrogenic event occurs in connection with the release of the bound phosphatidylserine to the cytoplasmic leaflet and support the hypothesis that the phospholipid interacts with specific lysine and arginine residues near the cytoplasmic border of the lipid bilayer during the translocation and reorientation required for insertion into the cytoplasmic leaflet.
ATP8A2是一种哺乳动物P4 - ATP酶（翻转酶），它将带负电荷的脂质底物磷脂酰丝氨酸从细胞膜的胞外侧小叶转运至胞质侧小叶。我们使用基于固体支持膜的电生理方法，研究了ATP8A2特定反应步骤的电生性，并探索了一条涉及带正电荷侧链残基的潜在磷脂转运途径。由突变引起的电流信号变化表明，主要的电生事件与结合的磷脂酰丝氨酸释放到胞质侧小叶有关，并支持以下假设：在磷脂插入胞质侧小叶所需的转运和重新定向过程中，磷脂与脂质双层胞质边界附近的特定赖氨酸和精氨酸残基相互作用。
