人間の触媒ステップIスプライソームの構造
Xiechao Zhan1, Chuangye Yan2, Xiaofeng Zhang1
1Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Science (New York, N.Y.)
|January 6, 2018
まとめ
研究 者 たち は 人間 の スプライソーム の 構造 を 決定 し た
科学分野:
- 分子生物学
- 構造生物学
- 生物化学
背景:
- スプライソームは,メッセンジャー前RNAのスプライシングを担う大きなリボ核タンパク質複合体である.
- スプライソームの組み立てと触媒は,ダイナミックな再配置と多数のタンパク質因子の作用を伴う.
- スプライソームの中間物質の構造を理解することは,スプライシングメカニズムを明らかにするために極めて重要です.
研究 の 目的:
- 人間のスプライソームの触媒ステップI (C) 複合体の高解像度冷凍電子顕微鏡構造を決定する.
- ヒトのC複合体と酵母複合体を比較し,タンパク質の組成の違いを特定する.
- C から C* への移行中のリボヌクレオプロテインの改造に関するメカニズム的な洞察を得る.
主な方法:
- ヒトのC複合体の構造を決定するために,冷凍電子顕微鏡 (cryo-EM) が使用された.
- 高解像度構造分析は,平均解像度4. 1アングストームで行われました.
- 人間のC複合体と酵母C複合体,そして人間のC複合体とC*複合体の比較構造分析が行われました.
主要な成果:
- 人間のC複合体の冷凍-EM構造は4. 1アングストームの解像度で決定された.
- 人間のC複合体は,Saccharomyces cerevisiae C複合体よりも11個のタンパク質を多く含んでいます.
- CCDC49/CCDC94とDEAHヘリカーゼPrp16の間の特定の相互作用が特定され,Prp16を活性部位RNA要素に橋渡しした.
結論:
- 研究結果は,ヒトと酵母のスプリセオソームのタンパク質組成の有意な違いを示しています.
- 特定された相互作用は,Prp16がRNAの再編成のためにどのように位置づけられているかについてのメカニズム的洞察を提供します.
- 構造的比較を基に,C*スプリセソーム複合体からC*スプリセソーム複合体への移行のための作業モデルが提案されています.
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