遗传编码 ε-N-甲烯氨酸到活细胞中的蛋白质中
Tian-Yi Zhu1,2, Shi-Yi Chen1,2, Mengdi Zhang1,2
1Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Science Institute, Zhejiang University, Hangzhou, Zhejiang, China.
Nature communications
|March 18, 2025
概括
研究人员确定了非希斯蛋白Cyclophilin A (CypA) 上的氨酸甲化 (Kmea). 这种翻译后的修改调节了细胞的氧化还原稳态,并且可以在活细胞中进一步修改.
科学领域:
- 生物化学和分子生物学
- 后翻译修改 后翻译修改
- 蛋白质组学是指蛋白质组学.
背景情况:
- 氨酸化是一种关键的翻译后修饰 (PTM),涉及多种细胞功能.
- 虽然已知有成千上万的氨酸化部位,但只有27个氨酸甲化部位 (Kmea) 已被确定,仅限于组织蛋白.
- 将Kmea与其同位素lysinecrotonylation (Kcr) 区分开来,带来了生化方面的挑战.
研究的目的:
- 为了识别非歇斯顿蛋白,Cyclophilin A (CypA) 上的Kmea位点.
- 调查Kmea在CypA中的功能性作用.
- 开发一种研究Kmea修饰及其在活细胞中的相互作用的方法.
主要方法:
- 在Cyclophilin A (CypA) 上确定Kmea的部位.
- 遗传密码扩展以将非正规氨基酸 (ncAA) ε-N-Methacryllysine (MeaK) 纳入目标蛋白.
- 亲和净化质谱 (MS) 用于识别与甲基化CypA.相互作用的蛋白质.
主要成果:
- 在非歇斯顿蛋白CypA.上确定了Kmea.
- 在CypA位点125的Kmea被发现可以调节细胞氧化还原平衡.
- 鉴定出HDAC1是CypA上的Kmea的调节者,基因编码的Kmea可以在活细胞中进一步甲基化为ε-N-甲基-ε-N-甲化 (Kmemea).
结论:
- 这项研究扩展了已知的Kmea修饰的风景,超越了基因组蛋白,将其扩展到非基因组蛋白,如CypA.
- 在CypA上,Kmea在调节细胞氧化还原平衡方面发挥着重要作用.
- 开发的遗传密码扩展方法为研究Kmea功能和交互 in vivo提供了一个强大的工具.
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