Shi Deling, Sheng Anran, Chi Lianli
National Glycoengineering Research Center, Shandong University, Qingdao, China.
Front Mol Biosci. 2021 Mar 9;8:639666. doi: 10.3389/fmolb.2021.639666. eCollection 2021.
Glycosaminoglycans (GAGs) are a family of linear and negatively charged polysaccharides that exist ubiquitously on the human cell surface as well as in the extracellular matrix. GAGs interact with a wide range of proteins, including proteases, growth factors, cytokines, chemokines and adhesion molecules, enabling them to mediate many physiological processes, such as protein function, cellular adhesion and signaling. GAG-protein interactions participate in and intervene in a variety of human diseases, including cardiovascular disease, infectious disease, neurodegenerative diseases and tumors. The breakthrough in analytical tools and approaches during the last two decades has facilitated a greater understanding of the importance of GAG-protein interactions and their roles in human diseases. This review focuses on aspects of the molecular basis and mechanisms of GAG-protein interactions involved in human disease. The most recent advances in analytical tools, especially mass spectrometry-based GAG sequencing and binding motif characterization methods, are introduced. An update of selected families of GAG binding proteins is presented. Perspectives on development of novel therapeutics targeting specific GAG-protein interactions are also covered in this review.
糖胺聚糖（GAGs）是一类线性且带负电荷的多糖家族，广泛存在于人类细胞表面以及细胞外基质中。GAGs与多种蛋白质相互作用，包括蛋白酶、生长因子、细胞因子、趋化因子和黏附分子，使其能够介导许多生理过程，如蛋白质功能、细胞黏附和信号传导。GAG - 蛋白质相互作用参与并干预多种人类疾病，包括心血管疾病、传染病、神经退行性疾病和肿瘤。过去二十年中分析工具和方法的突破有助于更深入地理解GAG - 蛋白质相互作用的重要性及其在人类疾病中的作用。本综述聚焦于人类疾病中GAG - 蛋白质相互作用的分子基础和机制方面。介绍了分析工具的最新进展，特别是基于质谱的GAG测序和结合基序表征方法。还介绍了选定的GAG结合蛋白家族的最新情况。本综述还涵盖了针对特定GAG - 蛋白质相互作用的新型治疗方法的发展前景。
