Hawkins Cheryl A, de Alba Eva, Tjandra Nico
Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 Center Drive, Bethesda, MD 20892, USA.
J Mol Biol. 2005 Mar 11;346(5):1381-92. doi: 10.1016/j.jmb.2004.12.045. Epub 2005 Jan 20.
Saposin C is a lysosomal, membrane-binding protein that acts as an activator for the hydrolysis of glucosylceramide by the enzyme glucocerebrosidase. We used high-resolution NMR to determine the three-dimensional solution structure of saposin C in the presence of the detergent sodium dodecyl sulfate (SDS). This structure provides the first representation of membrane bound saposin C at the atomic level. In the presence of SDS, the protein adopts an open conformation with an exposed hydrophobic pocket. In contrast, the previously reported NMR structure of saposin C in the absence of SDS is compact and contains a hydrophobic core that is not exposed to the solvent. NMR data indicate that the SDS molecules interact with the hydrophobic pocket. The structure of saposin C in the presence of SDS is very similar to a monomer in the saposin B homodimer structure. Their comparison reveals possible similarity in the type of protein/lipid interaction as well as structural components differentiating their quaternary structures and functional specificity.
鞘脂激活蛋白C是一种溶酶体膜结合蛋白，可作为葡糖脑苷脂酶水解葡糖神经酰胺的激活剂。我们使用高分辨率核磁共振（NMR）来确定在去污剂十二烷基硫酸钠（SDS）存在下鞘脂激活蛋白C的三维溶液结构。该结构首次在原子水平上展示了膜结合的鞘脂激活蛋白C。在SDS存在的情况下，该蛋白呈现出一种具有暴露疏水口袋的开放构象。相比之下，先前报道的在无SDS情况下鞘脂激活蛋白C的NMR结构是紧凑的，并且包含一个不暴露于溶剂的疏水核心。NMR数据表明SDS分子与疏水口袋相互作用。在SDS存在下鞘脂激活蛋白C的结构与鞘脂激活蛋白B同二聚体结构中的单体非常相似。它们的比较揭示了蛋白质/脂质相互作用类型以及区分其四级结构和功能特异性的结构成分方面可能存在的相似性。
