多蛋白组合在人类核糖体上协调共同翻译的酶处理
Marius Klein1, Klemens Wild1, Irmgard Sinning2
1Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120, Heidelberg, Germany.
Nature communications
|September 3, 2024
概括
从结构上发现了通过N-终端甲素切除 (NME) 和N-终端乙化 (NTA) 的两种共同翻译蛋白质修饰途径. 这些过程在核糖体上协调,独立于新生链,确保有效的蛋白质生物发生.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 新生蛋白质在翻译开始后立即经历酶性修饰.
- N-终端甲素切除 (NME) 和N-终端乙化 (NTA) 是在真核80S核糖体上常见的共同翻译性修饰.
- 在活性翻译过程中这些酶过程的协调仍然不清楚.
研究的目的:
- 阐明协调人类80S核糖体上N端甲酸切除 (NME) 和N端乙化 (NTA) 的结构机制.
- 研究甲氨基酸酶 (MAP1,MAP2) 和N-乙转移酶A (NatA) 如何与核糖体以及彼此相互作用.
- 了解新生多相关复合体 (NAC) 在协调这些修改中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定空缺的人类80S核糖体上的多酶复合物的结构.
- 结构分析的重点是NatA,MAP1,MAP2和NAC与核糖体的结合部位和相互作用.
- 该研究检查了这些因素与核糖体多蛋白道出口 (PTE) 和其他核糖体相关因素 (RAF) 的兼容性.
主要成果:
- 两个不同的结构组合揭示了80S核糖体上NME-NTA协调的两个途径.
- 这些组合独立于新生的多链形成.
- 纳塔利用一个距离结合点,容纳MAP1/MAP2和大多数RAF,而MAP2阻塞PTE,阻止NAC和MAP1的招募.
结论:
- 该研究为蛋白质生物发生过程中NME和NTA的协调编排提供了一个结构框架.
- NatA可以通过NAC与MAP1动态组装,这表明了一个协调的路径.
- MAP2与PTE的互动凸显了NME-NTA协调的另一种不兼容的途径.
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