鞘脂激活蛋白A和C的晶体结构。
Crystal structures of saposins A and C.
作者信息
Ahn Victoria E, Leyko Paul, Alattia Jean-René, Chen Lu, Privé Gilbert G
机构信息
Department of Medical Biophysics, University of Toronto, Canada.
出版信息
Protein Sci. 2006 Aug;15(8):1849-57. doi: 10.1110/ps.062256606. Epub 2006 Jul 5.
Abstract
Saposins A and C are sphingolipid activator proteins required for the lysosomal breakdown of galactosylceramide and glucosylceramide, respectively. The saposins interact with lipids, leading to an enhanced accessibility of the lipid headgroups to their cognate hydrolases. We have determined the crystal structures of human saposins A and C to 2.0 Angstroms and 2.4 Angstroms, respectively, and both reveal the compact, monomeric saposin fold. We confirmed that these two proteins were monomeric in solution at pH 7.0 by analytical centrifugation. However, at pH 4.8, in the presence of the detergent C(8)E(5), saposin A assembled into dimers, while saposin C formed trimers. Saposin B was dimeric under all conditions tested. The self-association of the saposins is likely to be relevant to how these small proteins interact with lipids, membranes, and hydrolase enzymes.
摘要
鞘脂激活蛋白A和C分别是半乳糖神经酰胺和葡萄糖神经酰胺溶酶体分解所必需的鞘脂激活蛋白。鞘脂激活蛋白与脂质相互作用，导致脂质头部基团对其同源水解酶的可及性增强。我们分别测定了人鞘脂激活蛋白A和C的晶体结构，分辨率分别为2.0埃和2.4埃，两者均显示出紧凑的单体鞘脂激活蛋白折叠结构。我们通过分析离心证实，这两种蛋白在pH 7.0的溶液中为单体。然而，在pH 4.8、存在去污剂C(8)E(5)的情况下，鞘脂激活蛋白A组装成二聚体，而鞘脂激活蛋白C形成三聚体。鞘脂激活蛋白B在所有测试条件下均为二聚体。鞘脂激活蛋白的自缔合可能与这些小蛋白如何与脂质、膜和水解酶相互作用有关。
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