Department of Biomedicine, University of Bergen, NO-5009 Bergen, Norway.
J Biol Chem. 2012 Jun 22;287(26):21950-6. doi: 10.1074/jbc.M112.350389. Epub 2012 May 3.
Heparan sulfate (HS) proteoglycans play critical roles in a wide variety of biological processes such as growth factor signaling, cell adhesion, wound healing, and tumor metastasis. Functionally important interactions between HS and a variety of proteins depend on specific structural features within the HS chains. The fruit fly (Drosophila melanogaster) is frequently applied as a model organism to study HS function in development. Previous structural studies of Drosophila HS have been restricted to disaccharide composition, without regard to the arrangement of saccharide domains typically found in vertebrate HS. Here, we biochemically characterized Drosophila HS by selective depolymerization with nitrous acid. Analysis of the generated saccharide products revealed a novel HS design, involving a peripheral, extended, presumably single, N-sulfated domain linked to an N-acetylated sequence contiguous with the linkage to core protein. The N-sulfated domain may be envisaged as a heparin structure of unusually low O-sulfate content.
硫酸乙酰肝素（HS）蛋白聚糖在多种生物学过程中发挥着关键作用，如生长因子信号转导、细胞黏附、创伤愈合和肿瘤转移。HS 与多种蛋白质之间的功能重要相互作用取决于 HS 链中的特定结构特征。果蝇（Drosophila melanogaster）常被用作研究 HS 在发育过程中的功能的模式生物。先前对果蝇 HS 的结构研究仅限于二糖组成，而不考虑通常在脊椎动物 HS 中发现的糖域排列。在这里，我们通过亚硝酸选择性解聚的方法对果蝇 HS 进行了生化特性分析。对生成的糖产物的分析揭示了一种新型的 HS 设计，涉及一个外围的、扩展的、可能是单一的、N-硫酸化的结构域，与核心蛋白的连接与 N-乙酰化序列相连。N-硫酸化结构域可以被设想为具有异常低的 O-硫酸化含量的肝素结构。
