エンドプラズマ網膜P5A-ATPaseは,トランスメブランヘリックス変位体である
Michael J McKenna1, Sue Im Sim2, Alban Ordureau1
1Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|September 25, 2020
まとめ
P5A-ATPaseトランスポーターSpf1は,エンドプラズマ網膜から標的を誤ったトランスメブランタンパク質を抽出します. この発見により タンパク質のターゲット設定のエラーを 修正する新しいメカニズムが明らかになりました
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- 臓器のアイデンティティは 精密なタンパク質の組成に依存しています
- 誤った標的タンパク質を臓器から除去するメカニズムは完全に理解されていません.
研究 の 目的:
- タンパク質品質管理におけるP5A-アデノシントリフォスファターゼ (ATPase) トランスポーターATP13A1 (Spf1) の役割を調査する.
- 誤った標的タンパク質が認識され,エンドプラズマ網膜 (ER) から除去される方法を明らかにする.
主な方法:
- 凍結電子顕微鏡を用いて,Saccharomyces cerevisiae Spf1の構造を決定した.
- Spf1とテール・アンクルドタンパク質のトランスメブランセグメントの相互作用を調査した.
- ERからのタンパク質抽出におけるP5A-ATPaseの活性が評価された.
主要な成果:
- Spf1は,尾を固定したタンパク質のトランスメブランセグメントと直接相互作用する.
- P5A-ATPaseの活性により,誤った標的タンパク質が ERから抽出されます.
- 構造分析により,アルファ-ヘリル型トランスメブランのセグメントを結合できる基板結合ポケットが明らかになった.
結論:
- P5A-ATPASEは ERから誤って挿入された水性ヘリクスを解き放つことができます.
- P5A-ATPaseによるこのTM脱位は,P型ATPase基板の新しいクラスを表しています.
- このメカニズムはタンパク質ターゲティングとトポゲネシスのエラーを修正する可能性があります.
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