绑定HP1染色体的结构与在lysine 9中甲基化的histon H3结合在一起
Peter R Nielsen1, Daniel Nietlispach, Helen R Mott
1Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Nature
|March 8, 2002
概括
异染色蛋白1 (HP1) 通过诱导适合机制来识别基因组修饰. 这种由芳香侧链形成的结合口袋对于理解表观遗传标记物识别和基因调节至关重要.
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
- 结构生物学 结构生物学
背景情况:
- 基因组基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因.
- 希斯H3氨酸9甲基化被色素蛋白1 (HP1) 识别,影响色素结构.
- HP1与甲基化组织蛋白结合对于控制基因表达和染色质组织至关重要.
研究的目的:
- 阐明HP1识别甲基化组素H3.3的结构机制.
- 为了识别HP1与海斯H3氨酸9甲基化结合的特定残留物和相互作用.
- 预测其他可能与甲基化蛋白结合的染色体,以及它们识别的基因.
主要方法:
- 进行X射线晶体学以确定HP1染色体结构的结构,与修改后的组素H3结合.
- 在结合口袋中的蛋白质-相互作用的分析.
- 对染色体序列进行比较分析以预测特异性.
主要成果:
- 惠普1利用诱导适合机制在氨酸9处结合二甲基化素H3.
- 三种芳香侧链 (Tyr21,Trp42,Phe45) 形成了N-甲基的结合口袋,在结合时变得有序.
- 特定的HP1残留物 (Val23, Leu40, Trp42, Leu58, Cys60) 与QTAR序列和Ala7相互作用,决定结合特异性.
结论:
- 这项研究揭示了HP1识别histon H3 lysine 9甲基化的精确结构基础.
- 这些发现提供了关于染色体结合口袋和特异性决定因素的保护性质的见解.
- 这项工作预测了其他染色体与甲基化蛋白质的潜在相互作用,促进了对表观遗传调节的理解.
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...