Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080, Bilbao, Spain.
J Membr Biol. 2014 Feb;247(2):155-65. doi: 10.1007/s00232-013-9619-7. Epub 2013 Dec 17.
Human phospholipid scramblase 1 (SCR) is a 318 amino acid protein that was originally described as catalyzing phospholipid transbilayer (flip-flop) motion in plasma membranes in a Ca²⁺-dependent, ATP-independent way. Further studies have suggested an intranuclear role for this protein in addition. A putative transmembrane domain located at the C terminus (aa 291-309) has been related to the flip-flop catalysis. In order to clarify the role of the C-terminal region of SCR, a mutant was produced (SCRΔ) in which the last 28 amino acid residues were lacking, including the α-helix. SCRΔ had lost the scramblase activity and its affinity for Ca²⁺ was decreased by one order of magnitude. Fluorescence and IR spectroscopic studies revealed that the C-terminal region of SCR was essential for the proper folding of the protein. Moreover, it was found that Ca²⁺ exerted an overall destabilizing effect on SCR, which might facilitate its binding to membranes.
人源磷脂翻转酶 1（SCR）是一种 318 个氨基酸的蛋白质，最初被描述为在 Ca²⁺依赖性、ATP 非依赖性的方式下催化质膜中磷脂的跨膜（翻转）运动。进一步的研究还表明该蛋白具有核内作用。位于 C 末端（aa 291-309）的假定跨膜结构域与翻转催化有关。为了阐明 SCR C 末端区域的作用，产生了一种突变体（SCRΔ），其中缺失了最后 28 个氨基酸残基，包括α-螺旋。SCRΔ失去了翻转酶活性，其对 Ca²⁺的亲和力降低了一个数量级。荧光和红外光谱研究表明，SCR 的 C 末端区域对于蛋白质的正确折叠是必需的。此外，还发现 Ca²⁺对 SCR 具有整体去稳定作用，这可能有助于其与膜结合。
