リシン9でメチル化されたヒストンH3に結合したHP1染色体の構造
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
まとめ
ヘテロクロマチンタンパク質1 (HP1) は,誘導適合メカニズムを使用してヒストンの改変を認識します. この結合ポケットは,アロマチックなサイドチェーンによって形成され,表遺伝子マーカーの認識と遺伝子調節を理解するために重要です.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
背景:
- ヒストンの改変は,DNA配列を変えることなく遺伝子発現を調節する重要な表遺伝子マーカーです.
- ヒストンH3ライシン9メチレーションは,クロマチン構造に影響を与えるヘテロクロマチンタンパク質1 (HP1) によって認識されます.
- メチル化ヒストンへのHP1結合は,遺伝子発現とクロマチンの組織を制御するために重要である.
研究 の 目的:
- HP1がメチルヒストンH3.3を認識する構造的メカニズムを解明する.
- ヒストンH3ライシン9メチル化にHP1の結合に関与する特定の残留物および相互作用を特定する.
- メチル化タンパク質と結合し得る他の染色体と,彼らが認識するモチーフを予測する.
主な方法:
- 改変ヒストンH3ペプチドに結合したHP1染色体の構造を決定するX線結晶学.
- 結合ポケット内のタンパク質-ペプチド相互作用の分析.
- 特殊性を予測するための染色体配列の比較分析.
主要な成果:
- HP1は,ヒストンH3をリシン9で二メチル化して結合させるための誘導適合メカニズムを使用します.
- 3つのアロマティックサイドチェーン (Tyr21,Trp42,Phe45) は,N-メチル群の結合ポケットを形成し,ペプチド結合時に順序付けられる.
- 特定のHP1残基 (Val23, Leu40, Trp42, Leu58, Cys60) は,QTAR配列とAla7と相互作用し,結合特異性を決定する.
結論:
- この研究は,ヒストンH3ライシン9メチル化に対するHP1の認識の正確な構造的基礎を明らかにしています.
- この発見は,染色体結合ポケットと特異性決定因子の保存性についての洞察を提供します.
- この研究は,他の染色体とメチル化タンパク質の潜在的相互作用を予測し,表遺伝的調節の理解を進めています.
関連する概念動画
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...