在p97/VCP适配器UBXD1驱动AAA+改造和环开放通过多域绑定交互驱动
Julian R Braxton1,2,3, Chad R Altobelli1,4, Maxwell R Tucker2,5
1Graduate Program in Chemistry and Chemical Biology, University of California San Francisco, San Francisco, CA, USA.
Nature structural & molecular biology
|November 9, 2023
概括
UBXD1适配器抑制了p97 ATPase活动,重塑了六合体结构. 这揭示了适配器如何控制p97功能在蛋白质稳态和细胞清除途径中的作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- p97 (含有氨酸的蛋白质) 是一个关键的AAA+ ATPase六合体,参与蛋白质稳态和宏分子分解.
- p97适配器调节其细胞功能,但它们对六合体的直接控制机制尚不清楚.
研究的目的:
- 研究UBXD1适配器在调节p97 ATPase活性和结构中的作用.
- 阐明UBXD1-介导的p97抑制的结构基础.
主要方法:
- 用X射线晶体学来确定人类p97-UBXD1复合物的结构.
- 位点定向突变发生,以评估UBXD1相互作用的功能影响.
- 生物化学试验测量p97 ATPase活动.
主要成果:
- UBXD1被确定为p97 ATPase活性的一种强有力的抑制剂.
- 结构分析显示,在p97六合体中存在大量的UBXD1接触,导致不对称的环开形状.
- 在UBXD1内保留的域和螺旋介导这些抑制相互作用.
结论:
- UBXD1作为p97的直接调节者,通过广泛的结构重塑来抑制其ATPase活性.
- 具有保留p97重塑图案的适配器在调节p97功能的过程中起着至关重要的作用.
- 了解这些相互作用为蛋白质稳态和细胞清除机制提供了洞察力.
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