Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 582,SE-751 23 Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 582,SE-751 23 Uppsala, Sweden.
Curr Opin Struct Biol. 2018 Jun;50:101-108. doi: 10.1016/j.sbi.2017.12.011. Epub 2018 Feb 9.
Glycosaminoglycans (GAGs) interact with a variety of proteins with important functions in development and homeostasis. Most of these proteins bind to heparin in vitro, a highly sulfated GAG species, although heparan sulfate and/or chondroitin/dermatan sulfate are more frequent physiological ligands. Binding affinity and specificity are determined by charge distribution, mainly due to sulfate and carboxylate groups and by GAG chain conformation. Interactions may be nonspecific, essentially reflecting charge density or highly specific, dependent on rare GAG-structural features. Yet other GAG epitopes bind protein ligands with intermediate specificity and variable affinity. Studies of heparan sulfate biosynthesis point to stochastic but strictly regulated, cell-specific polymer modification. Together, these features allow for graded modulation of protein functional response.
糖胺聚糖（GAGs）与多种具有发育和内稳态重要功能的蛋白质相互作用。这些蛋白质中的大多数在体外与肝素结合，肝素是一种高度硫酸化的 GAG 种类，尽管硫酸乙酰肝素和/或软骨素/透明质酸硫酸盐是更常见的生理配体。结合亲和力和特异性取决于电荷分布，主要归因于硫酸根和羧酸根以及 GAG 链构象。相互作用可能是非特异性的，本质上反映电荷密度，或者是高度特异性的，取决于罕见的 GAG 结构特征。还有其他 GAG 表位以中等特异性和可变亲和力结合蛋白配体。对硫酸乙酰肝素生物合成的研究表明，聚合物修饰具有随机性但受到严格调控，且具有细胞特异性。这些特征共同允许对蛋白质功能反应进行分级调节。
