Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., 2340, Beerse, Belgium.
VIB-UGent Center for Medical Biotechnology, B-9052 Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, B-9052, Ghent, Belgium.
Sci Data. 2023 Mar 6;10(1):121. doi: 10.1038/s41597-023-02009-1.
Heparan sulfates (HS) proteoglycans are commonly found on the cell surface and mediate many processes. Binding of HS ligands is determined by the sulfation code on the HS chain that can be N-/2-O/6-O- or 3-O-sulfated, generating heterogenous sulfation patterns. 3-O sulfated HS (3S-HS) play a role in several (patho)physiological processes such as blood coagulation, viral pathogenesis and binding and internalization of tau in Alzheimer's disease. However, few 3S-HS-specific interactors are known. Thus, our insight into the role of 3S-HS in health and disease is limited, especially in the central nervous system. Using human CSF, we determined the interactome of synthetic HS with defined sulfation patterns. Our affinity-enrichment mass spectrometry studies expand the repertoire of proteins that may interact with (3S-)HS. Validating our approach, ATIII, a known 3S-HS interactor, was found to require GlcA-GlcNS6S3S for binding, similar to what has been reported. Our dataset holds novel, potential HS and 3S-HS protein ligands, that can be explored in future studies focusing on molecular mechanisms that depend on 3S-HS in (patho)physiological conditions.
硫酸乙酰肝素（HS）蛋白聚糖通常存在于细胞表面，并介导多种过程。HS 配体的结合由 HS 链上的硫酸化编码决定，可进行 N-/2-O/6-O-或 3-O-硫酸化，产生异质的硫酸化模式。3-O 硫酸化的 HS（3S-HS）在几种（病理）生理过程中发挥作用，如血液凝固、病毒发病机制以及阿尔茨海默病中 tau 的结合和内化。然而，已知的 3S-HS 特异性相互作用物很少。因此，我们对 3S-HS 在健康和疾病中的作用的了解有限，尤其是在中枢神经系统中。我们使用人脑脊液，确定了具有特定硫酸化模式的合成 HS 的相互作用组。我们的亲和富集质谱研究扩展了可能与（3S-）HS 相互作用的蛋白质谱。通过验证我们的方法，发现抗凝血酶 III（ATIII）是一种已知的 3S-HS 相互作用物，其结合需要 GlcA-GlcNS6S3S，这与之前的报道相似。我们的数据集中包含新的、潜在的 HS 和 3S-HS 蛋白配体，可在未来的研究中探索，这些研究侧重于依赖（病理）生理条件下 3S-HS 的分子机制。
