通过硫素介导抑制NLRP1炎症体的结构基础
Zhikuan Zhang1, Takuma Shibata2, Akiko Fujimura1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Nature
|September 13, 2023
概括
硫素 (TRX) 结合并抑制NLRP1炎症酶,这是一个关键的炎症调节剂. 这一发现揭示了TRX作为先天免疫的内在检查点,
科学领域:
- 天生的免疫力
- 炎症组生物学
- 蛋白与蛋白的相互作用
背景情况:
- 炎症细胞是检测分子模式的重要免疫传感器,
- 在自身炎症性疾病和癌症中涉及NLRP1炎症酶过活化.
- 确切的NLRP1激活和调节机制仍然不完全理解.
研究的目的:
- 确定NLRP1炎症酶激活的内源调节剂.
- 阐明NLRP1的结构和功能基础.
主要方法:
- 用冷电子显微镜测定与硫素结合的人类NLRP1的结构.
- 针对NLRP1和人类氨酸的基因突变.
- 细胞测试以评估炎症酶激活和硫素的调节作用.
主要成果:
- 内源性硫素 (TRX) 被确定为NLRP1炎症体的直接结合剂和抑制剂.
- 冷-EM结构显示氧化TRX与NLRP1的核酸结合域子域结合.
- TRX的氧化还原活性囊对NLRP1的结合至关重要,而TRX则对NLRP1的激活产生负面调节.
结论:
- 硫素系统通过抑制NLRP1炎症酶激活,作为先天免疫的内在检查点.
- 这些发现提供了对NLRP1法规的机制理解.
- 在NLRP1介导疾病中,TRX-NLRP1相互作用是治疗干预的潜在目标.
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