SIRT6通过长链脂肪酸氨酸氨酸的水解来调节TNF-α分泌
Hong Jiang1, Saba Khan, Yi Wang
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Nature
|April 5, 2013
概括
人类SIRT6酶从蛋白质中去除脂肪基,揭示了调节蛋白质分泌的新机制,并提供了对翻译后修改的见解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 锡尔图因 (Sir2家族) 是依赖NAD的脱乙酶,参与转录,基因组稳定性,新陈代谢和寿命.
- 在七种哺乳动物 sirtuin 中,有四种在体外表现出较弱的 deacetylase 活性,这表明其具有替代功能.
- 蛋白质氨酸脂肪酸化是一种已知的哺乳动物修饰,其功能和调节尚未阐明.
研究的目的:
- 为了研究人类SIRT6除去乙化之外的酶活性.
- 阐明SIRT6在蛋白质翻译后修改中的作用.
- 了解蛋白质氨酸脂肪化对蛋白质氨酸的功能影响.
主要方法:
- 酶活性测试评估SIRT6去除脂肪基组的能力.
- 进行X射线晶体学以确定SIRT6基质特异性的结构基础.
- 生物化学实验以证明SIRT6对瘤亡因子-α (TNF-α) 分泌的作用.
主要成果:
- 人类SIRT6有效地从氨酸残留物中去除长链脂肪基.
- SIRT6的晶体结构显示出一个可容纳脂肪链的疏水口袋.
- 通过消除K19和K20残留物中的脂肪化,SIRT6促进TNF-α的分泌.
- 蛋白质氨酸脂肪化被确定为蛋白质分泌的新型调节机制.
结论:
- SIRT6具有显著的脂肪乙酶活性,与其已知的脱乙酶功能不同.
- 蛋白质氨酸脂肪酸化是一种新发现的调节蛋白质分泌的机制.
- 在脂肪化中SIRT6的作用为研究这个尚未探索的翻译后修饰开辟了新的途径.
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