与肝素硫酸盐的VSIG4相互作用抑制了VSIG4补充剂的结合
Sarah Y Ebstein1, Ashique Rafique1, Yi Zhou1
1Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, United States.
Glycobiology
|June 21, 2023
概括
含有V集和免疫球蛋白域4 (VSIG4),一个巨细胞免疫调节剂,与甲酸盐结合. 这种相互作用与补充蛋白竞争,揭示了VSIG4的新机制.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 含有V集和免疫球蛋白域4 (VSIG4) 是组织居民巨细胞上具有多种免疫功能的补充受体.
- 目前尚不完全了解VSIG4情境依赖性免疫调节的确切机制.
研究的目的:
- 确定VSIG4.4的新型约束合作伙伴.
- 阐明这些相互作用在VSIG4介导免疫调节中的作用.
主要方法:
- 遗传删除的肝素硫酸盐合成酶.
- 细胞表面肝硫酸盐的酶分裂.
- 具有约束力的测试来评估VSIG4-二甲酸相互作用.
- 致变性研究以确定结合表位.
- 竞争测试使用补充蛋白C3b和iC3b.
主要成果:
- 肝硫酸盐 (HS) 被确定为VSIG4.4的新型结合伙伴.
- 通过破坏HS合成或存在来减少VSIG4与细胞表面的结合.
- VSIG4直接与HS结合,显示对高硫酸和较长链的偏好.
- 在重叠的表位上,HS与C3b和iC3b在VSIG4结合方面竞争.
结论:
- 肝硫酸盐代表了一类新的VSIG4结合伙伴.
- 结合HS调节了VSIG4与补充蛋白的相互作用.
- 这一发现表明,可以通过硫酸肝素调节VSIG4免疫功能的新机制.
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