人体补充因子H中的SCR-17和SCR-18甘氨酸增强了其调节功能
Xin Gao1, Hina Iqbal2, Ding-Quan Yu2
1Division of Biosciences, Department of Structural and Molecular Biology, University College London, London, UK; Division of Medicine, University College London, London, UK.
The Journal of biological chemistry
|August 4, 2024
概括
人体补充因子H (CFH) 的糖化对SCR-17/18二元体的形成至关重要. 这种糖化增强了CFH与C3b的结合,这对宿主细胞保护至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 葡萄糖生物学 葡萄糖生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 人体补充因子H (CFH) 调节补充系统的激活,保护宿主细胞免受损伤.
- CFH包括20个短补体调节器 (SCR) 域和8个N-糖化位点.
- 之前的研究在SCR-17/18发现了CFH自我结合的部位,这对二元化至关重要.
研究的目的:
- 在CFH二分化中研究SCR-17/18上的N结合甘在CFH二分化中的作用.
- 确定糖基化是否影响CFH和C3b之间的相互作用.
- 阐明糖化对CFH调节功能的影响.
主要方法:
- 在大肠杆菌中含有或不含甘氨酸的SCR-17/18片段的表达.
- 从人体血和Pichia pastoris中净化全长CFH和C端碎片.
- 使用PNGase F.进行酶性脱糖化.
- 使用尺寸排除色谱和分析超离心法对二分化进行分析.
- 使用表面等离子体共振评估CFH与C3b的结合.
主要成果:
- 在缺乏甘氨酸的大肠杆菌中表达的SCR-17/18碎片没有形成二元体.
- 来自Pichia的脱糖化SCR-17/18碎片显示,二分体形成显著减少.
- 脱糖化全长CFH表现出对固定C3b.的结合亲和力降低.
- 糖化是SCR-17/18二元体形成所必需的,并增强了CFH的调节功能.
结论:
- 在SCR-17/18上,N链接的糖化对人体补充因子H的二分化至关重要.
- CFH的糖化增强了它与C3b的相互作用,从而改善了补充体的调节.
- 这项研究揭示了一种新的CFH调节机制,该机制依赖于糖化和二元化.
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