INO80染色体リモデレータとその核細胞複合体の構造とサブユニットトポロジー
Alessandro Tosi1, Caroline Haas, Franz Herzog
1Department of Biochemistry, Ludwig-Maximilian University, 81377 Munich, Germany; Gene Center, Ludwig-Maximilian University, 81377 Munich, Germany.
Cell
|September 17, 2013
まとめ
INO80染色体リモデレータの構造を決定し,その複数のサブユニット構造と核細胞に結合する方法を明らかにしました. これは,遺伝子調節とDNA修復におけるその役割を理解するための枠組みを提供します.
科学分野:
- 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
- バイオケミストリー バイオケミストリー
背景:
- INO80/SWR1染色体リモデレータは,転写とゲノム維持に不可欠な大型,複数サブユニット複合体です.
- これらの複合体は,H2AとH2A.Z.のようなヒストンの変異物を交換することによって,重要な細胞プロセスを促進します.
研究 の 目的:
- サッカロマイセス・セレヴィシア (Saccharomyces cerevisiae) INO80複合体の3次元構造を解明する.
- 核細胞結合の構造的基礎とクロマチンの改造の機能的意味を理解する.
主な方法:
- 統合的構造生物学アプローチは,冷凍電子顕微鏡,クロスリンク,質量スペクトロメトリを組み合わせたものです.
- サブユニット相互作用と核細胞結合ダイナミクスを特徴付けるための生化学的分析.
主要な成果:
- INO80の全体的な"胚形"アーキテクチャを決定し,異なる頭,首,体,足のモジュールを構成しました.
- 頭部にあるRvb1/Rvb2ヘテロドデカマー,足部にあるアクチン関連タンパク質 (Arp) を含む,主要なサブユニットの局所を特定した.
- ダイナミックなオープンとクローズドの形状を明らかにし,核細胞結合部位を頸部領域近くの凸した表面にマッピングしました.
結論:
- INO80クロマチンの改造器の詳細な構造的枠組みを確立しました.
- この重要なタンパク質複合体による核子の認識と再構成のメカニズムについての洞察を提供しました.
- 広範囲のINO80/SWR1染色体リモデレータファミリーに関する将来の研究のための基礎を築きました.
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...
02:54Nucleosome 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...
02:33The 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...
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...