ASK1的冷-EM结构揭示了一个不对称的架构,TRX1通过Allosterically调节TRX1
Karolina Honzejkova1, Dalibor Kosek2, Veronika Obsilova2
1Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague, Czech Republic.
亡信号调节激酶1 (ASK1) 是一个关键的压力传感器. 硫素1 (TRX1) 负面调节ASK1的结构和活性,提供潜在的抗炎治疗点.
科学领域:
- 分子生物学分子生物学
- 结构生物学是结构生物学.
- 生物化学 生物化学
背景情况:
- 亡信号调节酶1 (ASK1) 是一个关键的应激传感器,参与细胞过程,如亡和分化.
- ASK1的失调与各种疾病有关,包括癌症和炎症状况.
- 了解ASK1的结构调节对于开发向疗法至关重要.
研究的目的:
- 从结构上描述Apoptosis信号调节激酶1 (ASK1) 和其复合物与硫素1 (TRX1).
- 通过其二元化和蛋白质相互作用来阐明ASK1调节的机制性见解.
主要方法:
- 低温电子显微镜 (cryo-EM) 分析.
- 各种生物物理技术研究蛋白质结构和相互作用.
主要成果:
- ASK1形成一个紧的,不对称的二元在一个接近活跃的状态,稳定其活性激酶域通过域间和链间相互作用.
- 硫素1 (TRX1) 作为负效应因子,改变ASK1的结构,减少进入酶域的激活段.
- 结构性表征揭示了ASK1二元化和TRX1.1调节的关键见解.
结论:
- ASK1的二分化和域间接触对于稳定其活性构造至关重要.
- TRX1通过异质性修改其结构来负面调节ASK1的活动.
- 针对ASK1蛋白与蛋白相互作用,特别是TRX1,为抗炎疗法提供了一个有前途的战略.
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