结构可视化 HECT 型 E3 酶 Ufd4 接受和转移乌比奎以形成 K29/K48 分支的多聚乌比奎化
Xiangwei Wu1,2, Huasong Ai1, Junxiong Mao2
1Institute of Translational Medicine, School of Pharmaceutical Sciences, School of Chemistry and Chemical Engineering, National Center for Translational Medicine (Shanghai), Shanghai Key Laboratory for Antibody-Drug Conjugates with Innovative Target, Shanghai Jiao Tong University, Shanghai, China.
Nature communications
|May 9, 2025
概括
E3酶Ufd4产生K29/K48分支的泛素链,增强蛋白质降解. 结构分析揭示了Ufd4如何
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 乌比基因化是一种关键的翻译后修饰,它调节了蛋白质的稳定性和功能.
- 与K48结合的乌比奎丁链通常是蛋白质体降解的信号.
- 像K29/K48连接链这样的分支泛素链的形成,代表了更复杂的调节机制.
研究的目的:
- 阐明HECT-E3结合酶Ufd4调解K29/K48结合的泛化过程的机制.
- 确定Ufd4形成分支无处不在链的能力的结构基础.
主要方法:
- 生物化学试验用于研究无处不在活性.
- 生物物理技术以捕获结构快照的泛胺转移.
- 结构生物学方法可视化蛋白质与ubiquitin的相互作用.
主要成果:
- Ufd4在现有的K48链上优先催化K29结合的泛素化.
- 形成K29/K48分支的泛素链,作为增强的蛋白质降解信号.
- Ufd4 的 N-终端 ARM 区域和 HECT 域 C- 叶片对于招募 K48 结合 diubiquitin 和定位基质至关重要.
结论:
- Ufd4利用特定的结构元素来实现分支的无处不在.
- 这项研究提供了对由HECT型E3结合酶所产生的分支泛素链形成的机制和结构见解.
- 这项工作澄清了Ufd4在增强蛋白质降解途径中的作用.
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