Lindahl Ulf, Li Jin-ping
Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden.
Int Rev Cell Mol Biol. 2009;276:105-59. doi: 10.1016/S1937-6448(09)76003-4.
Heparan sulfate (HS) proteoglycans at cell surfaces and in the extracellular matrix of most animal tissues are essential in development and homeostasis, and variously implicated in disease processes. Functions of HS polysaccharide chains depend on ionic interactions with a variety of proteins including growth factors and their receptors. Negatively charged sulfate and carboxylate groups are arranged in various types of domains, generated through strictly regulated biosynthetic reactions and with enormous potential for structural variability. The level of specificity of HS-protein interactions is assessed through binding experiments in vitro using saccharides of defined composition, signaling assays in cell culture, and targeted disruption of genes for biosynthetic enzymes followed by phenotype analysis. While some protein ligands appear to require strictly defined HS structure, others bind to variable saccharide domains without any apparent dependence on distinct saccharide sequence. These findings raise intriguing questions concerning the functional significance of regulation in HS biosynthesis.
硫酸乙酰肝素（HS）蛋白聚糖存在于大多数动物组织的细胞表面和细胞外基质中，对发育和体内平衡至关重要，并在多种疾病过程中发挥不同作用。HS多糖链的功能取决于与多种蛋白质（包括生长因子及其受体）的离子相互作用。带负电荷的硫酸酯和羧基以各种类型的结构域排列，这些结构域通过严格调控的生物合成反应产生，具有巨大的结构变异性潜力。通过使用特定组成的糖类进行体外结合实验、细胞培养中的信号转导测定以及对生物合成酶基因进行靶向破坏并随后进行表型分析，来评估HS-蛋白质相互作用的特异性水平。虽然一些蛋白质配体似乎需要严格定义的HS结构，但其他配体则与可变的糖类结构域结合，而对特定的糖类序列没有明显依赖性。这些发现引发了关于HS生物合成调控功能意义的有趣问题。
