半乳糖凝集素是聚糖结合蛋白,将细胞糖缀合物的糖编码信息转化为生理活性,包括豁免权,细胞迁移,和信号。Galectins还与细胞外环境中的非糖基化伴侣相互作用,其中前B细胞受体(pre-BCR)在B细胞发育过程中。这些相互作用如何与半乳糖凝集素的聚糖解码功能相互作用尚不清楚。这里,我们在天然膜上进行NMR实验以监测Gal-1与生理细胞表面配体的结合。我们显示前BCR相互作用改变Gal-1与糖基化前B细胞表面受体的结合。在分子和细胞水平,我们将α2,3-唾液酸化基序鉴定为关键的靶向表位。这种靶向作用是通过选择性开关增加Gal-1与α2,3-唾液酸化的聚-N-乙酰基乳糖胺的接触而发生的。重要的是,我们观察到该开关参与了前BCR激活的调节。总之,这项研究表明,与非糖基化蛋白质的相互作用调节细胞表面半乳糖凝集素的聚糖解码功能。
Galectins are glycan-binding proteins translating the sugar-encoded information of cellular glycoconjugates into physiological activities, including immunity, cell migration, and signaling. Galectins also interact with non-glycosylated partners in the extracellular milieu, among which the pre-B cell receptor (pre-BCR) during B cell development. How these interactions might interplay with the glycan-decoding function of galectins is unknown. Here, we perform NMR experiments on native membranes to monitor Gal-1 binding to physiological cell surface ligands. We show that pre-BCR interaction changes Gal-1 binding to glycosylated pre-B cell surface receptors. At the molecular and cellular levels, we identify α2,3-sialylated motifs as key targeted epitopes. This targeting occurs through a selectivity switch increasing Gal-1 contacts with α2,3-sialylated poly-N-acetyllactosamine upon pre-BCR interaction. Importantly, we observe that this switch is involved in the regulation of pre-BCR activation. Altogether, this study demonstrates that interactions to non-glycosylated proteins regulate the glycan-decoding functions of galectins at the cell surface.