Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10
Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10
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DOI：
10.1016/j.isci.2020.101231
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发表时间：
2020-06-26
期刊：
影响因子：
5.8
通讯作者：
Silipo, Alba
中科院分区：
文献类型：
--
作者：
Forgione, Rosa Ester;Di Carluccio, Cristina;Silipo, Alba
Siglec-10是一种抑制性I型凝集素，选择性识别暴露在细胞表面上的唾液酸聚糖，参与几种病理生理过程。Siglec-10在调节免疫细胞功能中发挥的关键作用使其成为开发针对多种疾病的免疫治疗剂的潜在靶标。然而，该蛋白质的晶体结构目前尚未解析，Siglec-10与复杂聚糖相互作用的原子描述先前尚未解开。我们在这里提出了调节Siglec-10和天然存在的唾液酸聚糖之间相互作用的分子机制的第一个见解。我们使用组合的光谱、计算和生物物理方法来剖析聚糖的表位作图和结合后的构象，以提供3D复合物的描述。我们的研究结果提供了一个结构的角度来合理设计和开发高亲和力的配体来控制受体的功能。
Siglec-10 is an inhibitory I-type lectin selectively recognizing sialoglycans exposed on cell surfaces, involved in several patho-physiological processes. The key role Siglec-10 plays in the regulation of immune cell functions has made it a potential target for the development of immunotherapeutics against a broad range of diseases. However, the crystal structure of the protein has not been resolved for the time being and the atomic description of Siglec-10 interactions with complex glycans has not been previously unraveled. We present here the first insights of the molecular mechanisms regulating the interaction between Siglec-10 and naturally occurring sialoglycans. We used combined spectroscopic, computational and biophysical approaches to dissect glycans' epitope mapping and conformation upon binding in order to afford a description of the 3D complexes. Our outcomes provide a structural perspective for the rational design and development of high-affinity ligands to control the receptor functionality.