在人类calprotectin中Ca (II) 诱导的四聚化和过渡金属封存的分子基础
Robert Silvers1,2, Jules R Stephan3, Robert G Griffin3,4
1Department of Chemistry & Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.
Journal of the American Chemical Society
|October 26, 2021
概括
人类calprotectin (CP) 使用 (Ca(II)) 结合金属,对抗微生物. 结合将CP转移到不活跃状态和活跃状态之间,通过增强金属封存和抗菌活性来实现其免疫功能.
科学领域:
- 生物化学 生化学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 人类calprotectin (CP) 是一个关键的先天性免疫蛋白,参与金属封存.
- CP的抗菌功能依赖于 (Ca(II)) 结合和自我结合.
- 缺乏关于CP的异构体的apo形式的结构数据,阻碍了对其金属结合机制的理解.
研究的目的:
- 阐明与人类calprotectin (CP) αβ异构体结合的Ca(II) 的结构和动态影响.
- 了解 (II) 结合是如何促进CP向金属隔离活性状态的过渡.
主要方法:
- 使用溶液核磁共振 (NMR) 谱学研究了CP αβ异构体.
- 分析了Ca (II) 结合时的结构和动态变化.
主要成果:
- 二) 结合会诱导形状变化,有利于具有四化能力的"活性"状态.
- 二) 结合稳定了αβ异体聚合物,促进了 (αβ) 2异体聚合物的形成.
- 二) 结合通过局部和全效应组织了关键的金属结合点 (His3Asp和His6),包括在S100A9.9中稳定螺旋αIV.
结论:
- 二) 结合是CP激活和金属隔离功能的主要触发因素.
- 这项研究揭示了CP响应细胞外Ca (II) 进行宿主防御的分子机制.
- 了解这些结构动态,可以深入了解先天免疫力和金属平衡.
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