氧化后翻译性修改加速了calprotectin的蛋白质分解
Jules R Stephan1, Fangting Yu1, Rebekah M Costello1
1Department of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Journal of the American Chemical Society
|November 2, 2018
概括
人类calprotectin (CP) 的氧化修饰会影响其功能和寿命. 甲氨酸的氧化和二硫化键的形成改变了CP.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 蛋白质化学 蛋白质化学
背景情况:
- 人类calprotectin (CP) 是一种丰富的金属隔离蛋白质,对先天免疫和炎症至关重要.
- 通过限制转变金属对微生物病原体的可用性,CP在细胞外发挥作用.
- 在炎症部位的CP的命运和氧化修饰仍然不太清楚.
研究的目的:
- 研究氧化后翻译性修改对人类calprotectin (CP) 的生物物理和功能后果.
- 阐明甲氨酸氧化和二硫化键形成对CP的结构,金属结合,抗菌活性和降解的影响.
- 提出一种由活性氧物种调节的细胞外CP功能的更新模型.
主要方法:
- 使用15N标记CP-Ser.Ser.对人类CP的体内 metionin氧化的分析.
- 使用过氧化生成和检查复合CP-Ser与甲氨酸硫氧化物修饰.
- 评估过渡金属离子协调,抗菌活性,Ca (II) 诱导的四聚化和氧化CP的蛋白质分解.
- 在暴露于过氧化后,对本地CP中二硫化键形成的研究.
主要成果:
- 提出了令人信服的证据,证明了CP的体内 metionin氧化.
- 氧化后的CP物种保留了金属结合能力和抗菌活性.
- 在S100A9亚单元中甲81 (M81) 的氧化破坏了Ca (II) 诱导的四化并加速了降解.
- 在H2O2暴露时,本源CP中的二硫化键形成也加速了蛋白质分解的降解.
- 翻译后的氧化调节了CP的细胞外生命周期.
结论:
- 氧化后翻译性修改显著影响人类calprotectin的稳定性和功能.
- 由反应性氧物种引发的甲氨酸氧化和二硫化键形成,影响了CP的结构完整性和降解率.
- 这些发现扩展了细胞外CP的模型,突出了氧化作为炎症反应期间其寿命的关键调节者.
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