Li Miaomiao, Pedersen Lars C, Xu Ding
Department of Oral Biology, School of Dental Medicine, University at Buffalo, the State University of New York, Buffalo, NY, United States.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States.
Front Mol Biosci. 2023 May 19;10:1194293. doi: 10.3389/fmolb.2023.1194293. eCollection 2023.
Heparan sulfate-binding proteins (HSBPs) are structurally diverse extracellular and membrane attached proteins that interact with HS under normal physiological conditions. Interactions with HS offer an additional level of control over the localization and function of HSBPs, which enables them to behave in a more refined manner. Because all cell signaling events start at the cell membrane, and cell-cell communication relies on translocation of soluble factors across the extracellular matrix, HS occupies an apical position in cellular signal transduction by interacting with hundreds of growth factors, cytokines, chemokines, enzymes, enzyme inhibitors, receptors and adhesion molecules. These extracellular and membrane proteins can play important roles in physiological and pathological conditions. For most HS-binding proteins, the interaction with HS represents an essential element in regulating their normal physiological functions. Such dependence on HS suggests that manipulating HS-protein interactions could be explored as a therapeutic strategy to selectively antagonize/activate HS-binding proteins. In this review, we will discuss current understanding of the diverse nature of HS-HSBP interactions, and the latest advancements in targeting the HS-binding site of HSBPs using structurally-defined HS oligosaccharides and monoclonal antibodies.
硫酸乙酰肝素结合蛋白（HSBPs）是结构多样的细胞外和膜附着蛋白，在正常生理条件下与硫酸乙酰肝素（HS）相互作用。与HS的相互作用为HSBPs的定位和功能提供了额外的控制水平，使其能够以更精细的方式发挥作用。由于所有细胞信号事件都始于细胞膜，且细胞间通讯依赖于可溶性因子在细胞外基质中的转运，HS通过与数百种生长因子、细胞因子、趋化因子、酶、酶抑制剂、受体和黏附分子相互作用，在细胞信号转导中占据重要地位。这些细胞外和膜蛋白在生理和病理条件下均可发挥重要作用。对于大多数HS结合蛋白而言，与HS的相互作用是调节其正常生理功能的关键要素。对HS的这种依赖性表明，可探索通过操纵HS-蛋白相互作用作为一种治疗策略，以选择性地拮抗/激活HS结合蛋白。在本综述中，我们将讨论目前对HS-HSBP相互作用多样性的理解，以及使用结构明确的HS寡糖和单克隆抗体靶向HSBPs的HS结合位点的最新进展。
