Chondroitin sulfate (CS) is the placental receptor for the VAR2CSA malaria protein, expressed at the surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within the intervillous space by binding to a determinant in a 4-O-sulfated CS chains. However, the exact structure of these glycan sequences remains unclear. VAR2CSA-reactive CS is also expressed by tumor cells, making it an attractive target for cancer diagnosis and therapeutics. The identities of the proteoglycans carrying these modifications in placental and cancer tissues remain poorly characterized. This information is clinically relevant since presentation of the glycan chains may be mediated by novel core proteins or by a limited subset of established proteoglycans. To address this question, VAR2CSA-binding proteoglycans were affinity-purified from the human placenta, tumor tissues and cancer cells and analyzed through a specialized glycoproteomics workflow. We show that VAR2CSA-reactive CS chains associate with a heterogenous group of proteoglycans, including novel core proteins. Additionally, this work demonstrates how affinity purification in combination with glycoproteomics analysis can facilitate the characterization of CSPGs with distinct CS epitopes. A similar workflow can be applied to investigate the interaction of CSPGs with other CS binding lectins as well.

中文翻译：

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亲和色谱和糖蛋白组学工作流程，用于分析与胎盘和癌症中的疟疾 VAR2CSA 相互作用的硫酸软骨素蛋白聚糖。

硫酸软骨素 (CS) 是 VAR2CSA 疟疾蛋白的胎盘受体，在恶性疟原虫感染期间在受感染的红细胞表面表达。受感染的细胞粘附在合体滋养层细胞上或通过与 4- O 中的决定簇结合而被困在绒毛间隙内-硫酸化的 CS 链。然而，这些聚糖序列的确切结构仍不清楚。VAR2CSA 反应性 CS 也由肿瘤细胞表达，使其成为癌症诊断和治疗的有吸引力的靶点。在胎盘和癌组织中携带这些修饰的蛋白多糖的特征仍不清楚。此信息具有临床相关性，因为聚糖链的呈现可能由新的核心蛋白或有限的已建立蛋白聚糖的子集介导。为了解决这个问题，从人胎盘、肿瘤组织和癌细胞中亲和纯化了 VAR2CSA 结合蛋白聚糖，并通过专门的糖蛋白组学工作流程进行分析。我们表明 VAR2CSA 反应性 CS 链与异质性蛋白聚糖组相关联，包括新型核心蛋白。此外，这项工作证明了亲和纯化与糖蛋白质组学分析相结合如何促进具有不同 CS 表位的 CSPG 的表征。类似的工作流程也可用于研究 CSPG 与其他 CS 结合凝集素的相互作用。