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结构和功能表征的CREB结合蛋白 (CREBBP) 作为一个基因 propionyl转移酶

Guiling Cui¹, Marie Ley², Ariel E Mechaly³

¹Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France.

The Journal of biological chemistry

|July 4, 2025

概括

基因组 lysine propionylation 是一个关键的表观遗传标记. 这项研究表明,CREB结合蛋白 (CREBBP) 作为基因组 propionyl 转移酶,在体外和体内沉积H3K18Pr标记.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
分子生物学分子生物学
生物化学生化学

背景情况:

基因组 lysine propionylation是一种丰富的翻译后修饰,将细胞代谢和基因表达联系起来.
CREB-结合蛋白 (CREBBP) 和EP300是同源的基因素乙转移酶,在基因调节中起着关键作用.
虽然EP300的基转移酶活性是已知的,但CREBBP在此方面的功能仍然不太了解.

研究的目的:

为了研究CREBBP的潜在基因 propionyl转移酶活性.
为了阐明CREBBP的基因组 propionyl 转移酶功能的酶和结构基础.
提供关于CREBBP在将细胞代谢和表观遗传调节联系起来的作用的见解.

主要方法:

在体外乙转移酶试验中,使用各种基质和乙-CoA辅因子.
用,重组组素和重组核细胞体进行酶分析.
使用CRISPR-Cas9编辑细胞进行细胞研究.
人类CREBBP基因组酸转移酶域的晶体结构确定.

主要成果:

在实验室中,CREBBP表现出强大的基因组 propionyl 转移酶活性,特别是产生H3K18Pr标记.
细胞实验证实了CREBBP在体内作为基转移酶的作用,沉积了H3K18Pr标记.
晶体结构揭示了CREBBP与Propionyl-CoA和Lys-CoA相互作用的结构基础,支持其Propionyl转移酶功能.

结论:

除了其已知的乙转移酶功能外,CREBBP还具有显著的基因 propionyl转移酶活性.
这些发现扩大了我们对CREBBP酶谱及其在表观遗传调节中的作用的理解.
这项研究强调了CREBBP对通过基因素修饰连接细胞代谢和基因表达的机制的贡献.

关键词:

这就是CREBBP.克里斯普尔卡斯9 乙烯基转移酶的使用方法晶体结构晶体结构 lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation lysine propionylation 氨酸氨酸氨酸氨酸氨酸尼尔-CoA是一种蛋白质的乙化是蛋白质的

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