水和化物作为WNK激酶透感应过程中的全抑制剂
bioRxiv : the preprint server for biology
|September 11, 2023
概括
水分子和离子调节WNK激酶. 通过突变或PEG400破坏保存的水网络会改变WNK激酶活性和化物敏感性,这表明水作为一种全抑制剂.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 温克基因酶是通过化物和化压力调节的.
- 非化WNK1 (uWNK1) 形成了一个不对称的二元体,具有保存的水网络 (CWN1,CWN2).
研究的目的:
- 研究保存水网络和结在WNK激酶调节中的作用.
- 探索PEG400如何影响WNK1二元体结构和活性.
主要方法:
- 晶体学 WNK1 和 WNK3 激酶域.
- 在CWN1.1周围保存的带电残留物的位点定向突变发生.
- 生物化学测试以测量自酸化率和化物敏感性.
主要成果:
- PEG400破坏了uWNK1的二分体,水网络和结合.
- 保存的充电残留物中的突变改变了WNK1/WNK3自酸化和化物敏感性.
- 激活突变会诱导类似于PEG400效应的形状变化.
结论:
- 保存的水网络,特别是CWN1,在WNK激酶抑制中发挥着至关重要的作用.
- 水分子作为全联体起作用,调节WNK激酶活性.
- 水和化物调节机制相互连接.
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