干结合决定了Vibrio LuxR/HapR定数感应转录因子的蛋白质分解稳定性
bioRxiv : the preprint server for biology
|February 26, 2024
概括
硫胺与LuxR/HapR蛋白质结合,触发它们的降解,并控制Vibrio病原体中的毒性基因表达. 这项研究揭示了结合带的结合.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 卢克斯R/HapR蛋白质是TetR型的转录因子,调节了Vibrio物种中的毒性.
- 这些蛋白质有一个假定的连接体结合口袋,但尚未确定任何本源连接体.
- 带结合在LuxR/HapR功能中的作用仍然未知.
研究的目的:
- 为了研究连接体结合口袋在LuxR/HapR函数中的作用.
- 为了确定参与抑制剂结合的残留物,并了解抑制的机制.
主要方法:
- 使用硫胺胺抑制剂PTSP的结构功能分析.
- 前进基因查和X射线结晶学对PTSP结合的SmcR.
- 小角度X射线散射和计算建模.
- 通过ClpAP蛋白酶降解SmcR的体内研究.
主要成果:
- 在SmcR的连接体结合口袋中的八个残留物的替代减少了PTSP抑制.
- 结合PTSP会在N端DNA结合域中诱导全发展.
- 在生物体中,PTSP促进了ClpAP蛋白酶的SmcR降解.
- 与PTSP相互作用的残留物中的突变稳定了SmcR水平.
结论:
- 与LuxR/HapR蛋白质的联体结合促进了它们的蛋白质分解.
- 这种机制抑制了Vibrio病原体的下游毒性基因表达.
- 干结合是 LuxR/HapR 蛋白质稳定性和功能的关键媒介.
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