通过免疫抑制受体Siglec-10识别sialoglycan的结构基础
Elliot Medina1, Charlotte Mason2, Timothy H Tran3
1Department of Immunology, Moffitt Cancer Center, Tampa, FL 33612, USA; Cancer Biology PhD Program, University of South Florida, Tampa, FL 33612, USA.
Structure (London, England : 1993)
|February 26, 2026
概括
酸结合性免疫球蛋白类似的lectin 10 (Siglec-10) 结构揭示了它如何与化糖蛋白结合. 西格莱克-10的多元化和连接因子参与是其细胞表面相互作用的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 酸结合性免疫球蛋白类似的lectin 10 (Siglec-10) 是一种免疫抑制受体,可以识别化糖蛋白.
- 了解Siglec-10识别的分子基础对于阐明它在免疫调节中的作用至关重要.
研究的目的:
- 为了确定结合乳糖 (SL) 连接体的Siglec-10的结构.
- 为了可视化Siglec-10信号的基础分子识别事件,并确定关键的结构特征涉及连接体结合和同质化.
主要方法:
- 进行X射线晶体学以确定Siglec-10与sialyllactose复合体中的结构.
- 位点定向突变发生,以调查特定域和循环在连接体结合和同质化中的作用.
- 细胞结合试验评估突变和CD24淘汰对Siglec-10与乳腺癌细胞相互作用的影响.
主要成果:
- 这些结构显示,Siglec-10的域1 (D1) 通过非保留的CC'循环与SL接触.
- 西格莱克-10与α2,3和α2,6结合的SL结合,具有相似的亲缘关系.
- 西格莱克-10的同质化由疏水域2 (D2) 接口介导,这对于细胞结合至关重要.
- CD24淘汰并没有影响Siglec-10与乳腺癌细胞的结合,这表明具有更广泛的连接体识别特征.
结论:
- Siglec-10在D1中使用独特的CC'循环用于化糖蛋白识别.
- 通过D2接口进行Siglec-10的同质化对其功能至关重要.
- 西格莱克-10表现出比先前估计的更广泛的连接体识别概况,超过CD24.
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