通过辅助蛋白和棕化调节RAS棕甲基转移酶
Anlan Yang1,2, Shengjie Liu2,3, Yuqi Zhang2
1College of Life Sciences, Zhejiang University, Hangzhou, China.
Nature structural & molecular biology
|January 5, 2024
概括
研究人员发现了DHHC9-GCP16复合物如何催化RAS棕化. GCP16稳定了DHHC9,而脂结合和特定的氨酸棕化对酶活性至关重要,揭示了关键的调控见解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- HRAS和NRAS的棕化对于RAS信号传递至关重要.
- 与GCP16复合的DHHC9乙转移酶催化了这种关键的修饰.
- DHHC9活动和GCP16调节的确切机制尚不清楚.
研究的目的:
- 阐明DHHC9-GCP16复杂函数的结构基础.
- 了解GCP16在DHHC9-介导的棕细胞代谢中的作用.
- 确定调节DHHC9催化活性的关键因素.
主要方法:
- 人类DHHC9-GCP16和酵母Erf2-Erf4复合物的冷电子显微镜 (冷EM).
- 生物化学测试以评估催化活性.
- 现场定向突变发生,以调查基本残留物和区域.
主要成果:
- 冷电磁结构显示,GCP16稳定了DHHC9架构,而不是直接参与催化.
- 脂结合DHHC9的富含氨酸的区域对于活性至关重要.
- 在DHHC9上对特定的氨酸残留物 (C24,C25,C288) 的棕化对催化非常重要.
- GCP16还与DHHC14和DHHC18复合,这表明它在RAS棕化中起着更广泛的作用.
结论:
- GCP16 作为 DHHC9 的结构稳定剂,促进 RAS 棕化.
- DHHC9的特定结构特征和翻译后修饰是其催化功能的关键决定因素.
- 这些发现提供了对RAS棕甲基转移酶调节的机制性理解.
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