结合氨酸9甲基化素H3尾部的HP1染色体结构
Steven A Jacobs1, Sepideh Khorasanizadeh
1Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908-0733, USA.
Science (New York, N.Y.)
|February 23, 2002
概括
在HP1染色体内,HP1染色体结合了在lysine 9中甲基化的基因组H3尾巴,这对于表观遗传沉默至关重要. 结构分析揭示了这种相互作用,包括β链插入和芳香相互作用,如何影响结合亲和力.
科学领域:
- 结构生物学 结构生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 蛋白质-DNA相互作用
背景情况:
- 在表观遗传基因调节中,HP1 (Heterochromatin Protein 1) 蛋白质家族起着关键作用.
- 众所周知,HP1染色体因子会与基质化氨酸残留物结合,这些残留物存在于希斯尾部,特别是H3K9me.
- 这种相互作用对于建立和维持异色染色素,一种与基因沉默相关的染色素的凝缩形式,至关重要.
研究的目的:
- 阐明Drosophila HP1染色体和在lysine 9 (H3K9me) 中甲基化的组素H3尾之间的相互作用的结构和能量基础.
- 了解H3K9的不同甲基化状态 (二-与三甲基化) 如何影响结合亲和力和分子识别.
主要方法:
- 进行X射线晶体学以确定该综合体的高分辨率结构.
- 异热定位热量计 (ITC) 用于结合的能量分析.
- 位点定向突变发生,以探测特定残留物对结合的贡献.
主要成果:
- 基因素H3尾部采用β-链形态,完成HP1染色体的β-三明治结构.
- H3K9me的甲基团被精确地安置在由染色体的三个芳香侧链组成的子中.
- 邻近的残留物与染色体的一个面之间的特定接触介导了选择性识别.
- 与二甲基化 (H3K9me2) 相比,H3K9 (H3K9me3) 的三甲基化显示出略有改善的结合亲和力,这表明子-pi和范德瓦尔斯相互作用的作用.
结论:
- 这项研究提供了HP1染色体对H3K9me识别的详细分子机制.
- 这些发现强调了特定结构和能量特征在介导表观遗传沉默方面的重要性.
- 在H3K9me2和H3K9me3之间的结合亲和力中微妙的差异表明,在异色素蛋白形成中有一个微调的调节机制.
更多相关视频
24:02The ChroP Approach Combines ChIP and Mass Spectrometry to Dissect Locus-specific Proteomic Landscapes of Chromatin
Published on: April 11, 2014
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
相关概念视频
02:33The Nucleosome
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...
02:10The Nucleosome Core Particle
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.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
01:19The Nucleosome
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can 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.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
01:12The Nucleosome Core Particle
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...