交肉瘤X断点1蛋白质使用一个神秘的槽来选择性地识别H2AK119Ub核细胞组
Zebin Tong1, Huasong Ai2,3, Ziyu Xu1
1Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing, China.
Nature structural & molecular biology
|January 4, 2024
概括
突肉瘤 (Synovial Sarcoma) 是一个突肉瘤.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 结构生物学是结构生物学.
背景情况:
- 在SS18-SSX1蛋白驱动突肉瘤通过错位BAF复合体.
- SSX1对H2AK119Ub核细胞的识别是至关重要的,但在机制上不清楚.
- 在SSX1中缺乏正规的泛胺结合域,这给我们带来了一个难题.
研究的目的:
- 阐明SSX1识别H2AK119Ub核细胞的机制.
- 为了确定SSX1-核相互作用的结构基础.
- 了解这种相互作用如何促进突肉瘤病变的发生.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与H2AK119Ub核体结合的SSX1的结构.
- 在体外生化测试以验证结合相互作用.
- 细胞测试以评估功能后果.
主要成果:
- 确定了SSX1与H2AK119Ub核细胞结合的3.1-Å cryo-EM结构.
- 发现了一种独特的结合模式,涉及核酶体上神秘的基本槽,独立于正规的泛素结合域.
- 证明SSX1结合会诱导DNA在核细胞进出口部位的解封.
结论:
- SSX1采用一种非常规的机制来识别无处不在的核细胞.
- 这种独特的认可促进了BAF综合体对波利康布镇压地区的异常招募.
- 这些发现为SS18-SSX1驱动的突瘤发生在突肉瘤提供了洞察力.
相关概念视频
Nucleosome Remodeling
9.1K
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...
9.1K
Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K
Histone Modification
13.3K
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...
13.3K
The Nucleosome
16.3K
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
16.3K
The Nucleolus
8.9K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.9K
The Nucleosome Core Particle
918
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...
918


