在SETDB蛋白质的非正规甲基-CpG结合域和C11orf46之间的蛋白质-蛋白质相互作用的结构证据
Yutaka Mahana1, Mariko Ariyoshi2, Ryu-Suke Nozawa3
1Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-Ku, Kyoto 615-8510, Japan.
Structure (London, England : 1993)
|December 30, 2023
概括
参与表观遗传基因沉默的SETDB1和SETDB2蛋白质具有非正规的甲基-CpG结合域 (MBD). 这些MBD与像C11orf46这样的蛋白质相互作用,而不是DNA,揭示了基因调节中的新角色.
科学领域:
- 表观遗传学和染色体生物学
- 结构生物学是结构生物学.
- 基因调节的分子机制
背景情况:
- SETDB1和SETDB2是关键的表观遗传调节者,它们调解了素H3氨酸9三甲基化 (H3K9me3).
- 它们的非正规甲基-CpG结合域 (MBDs) 表明其除了DNA甲基化之外的功能,可能涉及蛋白质相互作用.
- 了解SETDB2的MBD结构对于破译其在抑制色素复合体中的作用至关重要.
研究的目的:
- 为了确定人类SETDB2 MBD与其结合伙伴C11orf46.6的复合体中的晶体结构.
- 阐明SETDB2 MBD和C11orf46.6之间的相互作用的分子基础.
- 研究SETDB1/2蛋白质中非正规MBD的功能影响.
主要方法:
- 进行X射线晶体学以确定SETDB2 MBD-C11orf46复合物的结构.
- 生物化学测试以表征相互作用接口.
- 结构分析,以确定关键的相互作用残留物和基因.
主要成果:
- 晶体结构显示SETDB2 MBD与C11orf46.6的氨酸丰富域结合.
- 尽管MBD核心具有DNA结合表面,但通过其N端延伸和氨酸指纹图案与C11orf46相互作用.
- 分子间β片形成有助于复合体的稳定性.
- 非正规的MBD似乎已经失去了DNA结合能力,而是调解蛋白质-蛋白质相互作用.
结论:
- 在SETDB2 MBD的功能作为一个蛋白质-蛋白质相互作用模块,而不是一个DNA结合域.
- 这种与C11orf46的相互作用是由SETDB2 MBD独特的结构特征介导的.
- 结果提供了关于SETDB相关基因抑制复合物的组装和MBDs的演变的见解.
相关概念视频
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K