ER膜の翻訳後のタンパク質転位機構の構造
Xudong Wu1,2, Cerrone Cabanos1,2, Tom A Rapoport3,4
1Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.
Nature
|January 16, 2019
まとめ
Sec62-Sec63複合体は,冷凍-EM構造分析によって明らかになったように,その横のゲートを開くことで,翻訳後のタンパク質転位のためのSec61チャネルを活性化します. このメカニズムは,高度に水害性の信号配列が欠けているタンパク質の通過を容易にする.
科学分野:
- 分子生物学
- 構造生物学
- 細胞生物学
背景:
- 細胞機能にはタンパク質の転位が不可欠であり,ユーカリオットではSec61チャンネル,プロカリオットではSecYチャンネルが関与する.
- 信号配列の水嫌性が異なるタンパク質は,共同翻訳経路とポスト翻訳経路を含む異なる転位経路を利用する.
- Sec62- Sec63複合体は,ユカリオットにおける翻訳後の転位を媒介することが知られているが,Sec61チャネル活性化のメカニズムは不明のままである.
研究 の 目的:
- Sec62-Sec63複合体が,翻訳後のタンパク質転位のためのSec61チャネルを活性化する構造的メカニズムを解明する.
- Saccharomyces cerevisiaeのタンパク質転位に関与する完全なSec複合体の構造を決定する.
主な方法:
- 電子冷凍顕微鏡 (cryo-EM) を用いてSec複合体の高解像度構造を決定した.
- Sec61,Sec62,Sec63,Sec71,Sec72の相互作用を調査するために生化学的および構造的分析が使用されました.
主要な成果:
- 構造は,Sec63がSec61チャンネルと直接相互作用し,プラグドメインを異動させずにサイドゲートの広い開口を誘導することを明らかにします.
- この横のゲート開口は,低水嫌性の信号配列を脂質相に挿入するためにSec61チャネルをプリムします.
- Sec63の細胞塩基Brlドメインはリボソーム結合を阻害し,ポリペプチドの捕獲に関与するSec71とSec72を誘導することが示された.
結論:
- この研究は,Sec62-Sec63複合体がSec61経路を翻訳後の転移にどのように活性化させるかを理解するための構造的基礎を提供します.
- 発見は,真核細胞のタンパク質標的化に不可欠なチャネルゲートと基板捕獲の新しいメカニズムを明らかにしています.
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