SIRT7核细胞参与和基质特异性的结构基础
Carlos Moreno-Yruela1, Babatunde E Ekundayo2,3, Polina N Foteva4
1Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), School of Basic Sciences (SB), EPFL, Lausanne, Switzerland. carlos.morenoyruela@epfl.ch.
Nature communications
|February 3, 2025
概括
一种与癌症相关的酶SIRT7修改了histon H3K36和H3K18. 我们的研究揭示了它的核细胞结合和特异性,使得工程选择性能够用于治疗开发.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 染色体修饰酶通过向基因子残留物来调节基因表达.
- 赛尔图因7 (SIRT7) 是一种NAD+依赖的脱酶,涉及癌症,已知在核细胞上脱H3K36和H3K18.
研究的目的:
- 阐明SIRT7对H3K36和H3K18脱基化的特异性的结构基础.
- 了解SIRT7如何在结构层面与核细胞相互作用.
主要方法:
- 基于机制的交叉链接战略
- 低温电子显微镜 (cryo-EM) 是一种电子显微镜.
- 酶和细胞测试试验.
主要成果:
- 确定了核细胞结合SIRT7的结构,揭示了其独特的N端核细胞结合域和催化域相互作用部位.
- SIRT7对H3K36和H3K18表现出不同的结合姿势,诱导了酶和核细胞体的结构变化.
- 这项研究揭示了SIRT7氨酸特异性的结构性决定因素.
结论:
- 这些发现为SIRT7的核细胞识别和脱特异性的结构性理解提供了帮助.
- 开发了具有增强H3K18ac选择性的工程SIRT7变体.
- 这项工作为设计SIRT7活性小分子调节器奠定了基础.
相关概念视频
The Nucleosome Core Particle
847
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
847
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Covalently 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
Nucleosome Remodeling
8.9K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
8.9K
Histone Modification
13.0K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.0K
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K


