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膜内チャペロン複合体は,膜タンパク質の生殖を促進する
Patrick J Chitwood1, Ramanujan S Hegde2
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|August 21, 2020
まとめ
研究者らはPAT複合体を発見しました ER-レジデントのタンパク質複合体で 膜内チャペロンとして機能します 組立中のトランスメブラン領域を保護し,誤った折り畳みを防止し,タンパク質ホメオスタシスを維持します.
科学分野:
- 細胞生物学
- 分子生物学
- タンパク質の生化学
背景:
- 統合膜タンパク質は遺伝子の約25%を構成し,エンドプラズマ網膜 (ER) で処理される.
- 単一トランスメブランドメイン (TMD) を標的にして挿入するメカニズムは知られているが,多スパンプ膜タンパク質の組み立ては十分に理解されていない.
- TMD の水性アミノ酸は,生殖過程でチャペロニングを必要としますが,ER 居住の膜内チャペロンはほとんど定義されていません.
研究 の 目的:
- マルチスパンディング膜タンパク質の組み立てに関与する ER-レジデントの膜内チャペロンを特定し,特徴づけること.
- 脂質二重層内のトランスメブランドメインの保護と折りたたみにおける新しいチャペロンの役割を解明する.
主な方法:
- CCDC47とAsterixのヘテロダイマーであるPAT複合体の識別
- 新生トランスメブラン領域 (TMDs) とのPAT複合体の関与の分析.
- PAT複合体のサブユニットがない細胞における多スパンプ膜タンパク質バイオゲネシスの評価.
主要な成果:
- CCDC47とAsterixで構成されるPAT複合体は,豊富なER居住性膜内シェパロンとして特定されています.
- PAT複合体は,脂質二重層内の非シールド化サイドチェーンで新生TMDに結合する.
- PAT複合体のいずれかのサブユニットの喪失は,多重スパンディング膜タンパク質の生体生成を阻害する.
結論:
- PAT複合体は,多スパンプ膜タンパク質の組み立て中に不可欠な膜内チャペロンとして機能する.
- このチャプロン活動はTMDを保護し,誤った折り畳みを最小限に抑え,細胞タンパク質ホメオスタシスに不可欠です.
- PAT複合体の発見は 膜タンパク質の生体形成の基本的プロセスに 新たな洞察をもたらします
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