在Siglec-8/9/3的CC'循环中的序列多样性决定了对硫酸寡糖的识别
Yucheng Wang1, Yujie Peng1,2, Rui Long1,2
1Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Computational and structural biotechnology journal
|September 7, 2023
概括
西格莱克免疫受体通过识别特定的糖结构来调节细胞功能. 分子建模揭示了Siglec CC中的变异如何发生.
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:
- 西格莱克是免疫细胞的莱克,通过结合化甘氨酸来调节免疫反应.
- 西格莱克-8,西格莱克-9和西格莱克-3表现出硫酸基N-乙酸氨 (sLacNAc) 的特异性.
- 锡格莱克斯的CC循环区域参与确定硫酸寡糖的结合特异性.
研究的目的:
- 通过Siglec-8,Siglec-9,Siglec-3.0来研究硫化sLacNAc的差异识别的结构基础.
- 阐明CC'循环残留物在与硫酸寡糖的相互作用中介作用.
主要方法:
- 用分子建模研究来分析结合相互作用.
- 分析的重点是Siglec-8,Siglec-9和Siglec-3的CC'循环残留物.
- 研究了sLacNAc在银河糖和/或N-乙葡萄糖胺上对6-硫酸的识别.
主要成果:
- 西格莱克-9的负电荷的CC'循环残留物引起了6硫酸银河糖的排斥,阻止了识别.
- 西格莱克-8的带正电荷的CC'循环残留物与6硫酸银河糖形成了有利的相互作用,赋予了高特异性.
- 由于中性CC'循环残留物,Siglec-3展示了一种双硫酸sLacNAc的双态结合模型,允许不同的结合姿势.
结论:
- 在Siglec-8,Siglec-9,Siglec-3中的CC'循环序列变异为硫酸寡糖的差异识别提供了一个结构机制.
- 这些发现提供了关于Siglecs的约束特征及其在免疫中的调控作用的见解.
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