在心血管发育中,N端 arginylation 的重要作用
Yong Tae Kwon1, Anna S Kashina, Ilia V Davydov
1Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|July 6, 2002
概括
Arg-tRNA-蛋白转移酶 (R-转移酶) 基因ATE1对于胚胎发育,特别是心脏形成至关重要. 它的 arginylation 路径起到氧气传感器的作用,氧化cysteine 在 arginylation 之前.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 该N端规则通路通过N端氨基酸调节蛋白质降解.
- 由Arg-tRNA蛋白转移酶 (R-转移酶) 介导的阿尔基尼化向特定的N端残留物,如阿斯巴甜酸,谷氨酸和氨酸.
- 在哺乳动物中,ATE1基因编码了这些R转移酶.
研究的目的:
- 研究ATE1基因在哺乳动物发育中的功能.
- 阐明N端 arginylation在蛋白质降解和细胞过程中的作用.
- 为了确定 arginylation 路径是否可以作为氧气传感器.
主要方法:
- 产生缺乏ATE1 (ATE1-/-) 的小鼠菌株.
- 对ATE1-/-胚胎的表型分析,重点关注心脏发育和血管重塑.
- 生物化学试验研究N端 arginylation的机制,包括基质氧化.
主要成果:
- 由于心脏发育和血管再生的严重缺陷,ATE1-/-胚胎表现出胚胎致死性.
- 生物化学分析显示,N端的氨酸在化之前被氧化.
- 这种氧化依赖的 arginylation 与 N-终端阿斯巴酸盐和谷氨酸酸的直接 arginylation 相反.
结论:
- ATE1基因及其编码的R转移酶对胚胎的生存,心脏发育和血管形成至关重要.
- 涉及先前氧化的N端半氨酸的化,表明一种新的调节机制.
- N端规则路径的化分支可能作为生物氧传感器起作用.
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