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人間のDOT1Lの触媒ドメインの構造は,SETドメイン以外の核細胞ヒストンメチルトランスフェラーゼである
Jinrong Min1, Qin Feng, Zhizhong Li
1W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell
|March 12, 2003
まとめ
研究者らはヒトのDot1-like (hDOT1L) と呼ばれる独特のヒストンメチルトランスフェラーゼの構造を明らかにした. この研究は,hDOT1Lを明らかにしています.
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:
- Dot1はヒストンメチルトランスフェラーゼであり,ヒストンH3をライシン-79.9でメチル化する.
- 他の既知のヒストンメチルトランスフェラーゼとは異なり,Dot1はSETドメインを欠いており,特に核体ヒストンH3を標的としています.
- Dot1のユニークなメカニズムを理解することは,表遺伝的調節の洞察にとって極めて重要です.
研究 の 目的:
- S-アデノシル-L-メチオニン (SAM) 複合体によるヒトドット1型 (hDOT1L) の触媒領域の高解像度結晶構造を決定する.
- hDOT1Lのユニークな触媒機構の構造的基礎と,核細胞基板に対する特異性を明らかにする.
- エピジェネティック・レギュレーションにおけるDot1タンパク質の機能に関するメカニズム的な洞察を提供するため.
主な方法:
- X線結晶学を用いて,SAMに結合したhDOT1L触媒ドメインの2.5 Å解像度構造を解明した.
- 核細胞結合と酵素活性における異なるタンパク質領域の役割を評価するために生化学的測定を行った.
- 分子モデリングは,触媒機構と基板特異性をさらに調査するために使用されました.
主要な成果:
- 解かれた構造は,アルファヘリカルなN端領域と中央のアルファ/ベータ構造を特徴とするhDOT1Lのユニークなアーキテクチャを明らかにします.
- 重要な構造的特徴には,定義されたSAM結合ポケットとライシン基板結合のための潜在的なチャネルが含まれています.
- 柔軟で陽性電荷のC端領域は,核細胞結合と触媒活動の両方にとって重要であると特定されました.
結論:
- 構造的および生化学的なデータは,hDOT1Lがヒストンメチルトランスフェラーゼとしてどのように機能するかについての重要なメカニズム的な洞察を提供します.
- この発見は,Dot1タンパク質のユニークな構造組織と基板認識機構を強調しています.
- この研究は,この重要な表遺伝子調節体の触媒機構と核細胞特異性についての理解を前進させる.
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...
02:32Histone 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,...
02:38Heterochromatin
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...
02:32Histone 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,...
01:19The 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...