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Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria
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TIM23複合体によるミトコンドリアタンパク質輸入の構造的基礎
Sue Im Sim1, Yuanyuan Chen1,2, Diane L Lynch3,4
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Nature
|June 21, 2023
まとめ
TIM23複合体はミトコンドリアにタンパク質を輸入する. 構造的な研究により,タンパク質の転位チャネルは Tim17で,Tim23ではないことが明らかになり,ミトコンドリアタンパク質の輸入に関する以前のモデルに異議を唱えた.
科学分野:
- ミトコンドリア生物学
- 分子細胞生物学
- タンパク質の輸入メカニズム
背景:
- ミトコンドリアは 細胞溶液から何千ものタンパク質を 輸入します
- TIM23複合体は,ミトコンドリアマトリックスと内膜にタンパク質を輸入するために不可欠です.
- TIM23サブユニット,特にTim23とTim17によるタンパク質転移の正確なメカニズムは,構造的に定義されていないままでした.
研究 の 目的:
- TIM23複合体によるタンパク質転位の構造的基礎を解明する.
- タンパク質伝導チャネルの形成におけるTim23とTim17の役割を解明する.
- ミトコンドリアタンパク質の輸入のための改訂モデルを提案する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) で,コアTIM23複合体の構造を決定する.
- タンパク質の転位経路を調査する生化学分析
主要な成果:
- ヘテロトリメリックのTim17-Tim23-Tim44複合体の冷凍-EM構造を決定した.
- 前のモデルと違って,Tim23とTim17は単一のチャネルを形成せず,別々の対極の空洞を持っています.
- Tim23ではなくTim17の穴がタンパク質の転位経路として機能し,Tim23は構造的な役割を果たしている可能性が高い.
- サブユニットMgr2は,ポリペプチド転位中にTim17腔の横開口をシールすることが観察されました.
結論:
- Tim23とTim17が直接のタンパク質チャネルを形成するという一般的なモデルは誤っている.
- Tim17は機能的転位孔を形成し,Tim23は構造的または規制的な機能を果たしている可能性が高い.
- Mgr2によるサブユニットと潜在的なシーリングの異なる役割を含む,TIM23媒介のタンパク質輸入のための新しいモデルが提案され,ミトコンドリアの生体生成に関する私たちの理解を前進させています.
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Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
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