ヒストンメチルトランスフェラーゼSET7/9の結晶構造と機能分析
Jonathan R Wilson1, Chun Jing, Philip A Walker
1Structural Biology Group, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
Cell
|October 10, 2002
まとめ
ヒストンのメチル化はクロマチンの構造を調節する. 研究者らはヒトのSET7/9の結晶構造を解明し,ヒストンH3ライシン-4メチル化とコファクター結合のための重要な残基を特定しました.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- エピジェネティクス エピジェネティクス
背景:
- ヒストンのメチル化は,クロマチンの構造を調節するために極めて重要です.
- SETドメインはヒストンリシンメチルトランスファーゼで一般的です.
研究 の 目的:
- 人間のSET7/9断片の結晶構造を決定する.
- ヒストンH3ライシン-4メチル化に不可欠な残基を特定するために.
- コファクター (AdoMet) の結合および触媒メカニズムを理解する.
主な方法:
- 人間のSET7/9断片のX線結晶学.
- サイト・ディレクテッド・ミュータジェネシス.
- 酵素活性と基板相互作用に関する生化学的測定.
主要な成果:
- 結晶構造は,N端ベータシートとSETドメインを明らかにした.
- ヒストンH3リジン-4の触媒活性に不可欠な2つのC端末残基が特定されました.
- コファクターAdoMetの結合モードが解明されました.
- カタリシス,AdoMet結合,および基板相互作用における不変残留物の役割は,生化学データによって支持されました.
結論:
- この研究は,SET7/9機能に関する構造的および生化学的洞察を提供します.
- SET7/9メカニズムを理解することは,表遺伝的調節を理解するのに役立ちます.
- この研究は,標的治療法の開発に役立つかもしれない.
関連する概念動画
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...
02:54Nucleosome Remodeling
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...
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:32Histone Modification
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 deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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...