INO80複合体によるATP依存クロマチン再構成の構造的基礎
Sebastian Eustermann1,2, Kevin Schall1,2, Dirk Kostrewa1,2
1Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Nature
|April 13, 2018
まとめ
INO80複合体は,ATPに依存するモーターを使用して核細胞をスライドし,遺伝子発現を調節します. この研究は その構造を明らかにし クロマチンを再構成するために DNAとヒストンをどのように 握っているかを示しています
科学分野:
- 構造生物学
- クロマチン生物学
- 分子 機構
背景:
- ユカリオット核のDNAは,INO80複合体のようなATP依存の染色体リモデラーによって位置づけられ,ヌクレオソームに詰め込まれています.
- INO80複合体は,ニュクレオソームスライディングとヒストン交換を通じて遺伝子発現,DNA修復,複製に影響を与えますが,その構造的メカニズムはまだ不明です.
研究 の 目的:
- ニュクレオソームに結合したINO80複合体の高解像度冷凍電子顕微鏡構造を決定する.
- INO80媒介による核細胞のスライディングとヒストンの交換の背後にある分子メカニズムを解明する.
主な方法:
- 原子核に結合したChaetomium thermophilumのINO80核複合体の冷凍電子顕微鏡 (冷凍EM)
- 構造データを既存の生化学データと統合し,メカニズムモデルを提案する.
主要な成果:
- INO80の核構造は 核細胞と広範囲にわたる接触を明らかにし DNAの1つの渦を揺るがしています
- Rvb1/Rvb2 AAA+ヘテロヘクサマーが脚架とステータとして機能し,Swi2/Snf2 ATPaseモーターはDNAを解き放ち,ヒストン-DNAの接触を妨害する.
- Arp5とIes6は,Arp5のグラッパードメインが核分裂体を結合し,エントリーDNAに接続することで,対グリップとして作用する.
結論:
- INO80による核細胞のスライディングとヒストンの編集のための統一メカニズムが提案されており,ATPaseモーターによって駆動されるマクロ分子ラッチが含まれています.
- モーターはArp5のグリップに対してDNAを継続的にポンプし,一時的なH2A-H2B曝露を通じて転位ステップと潜在的なヒストン交換につながります.
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