マラリア寄生虫のトランスロコン構造とエフェクター輸出のメカニズム
Chi-Min Ho1,2,3, Josh R Beck4,5,6, Mason Lai2
1The Molecular Biology Institute, University of California, Los Angeles, CA, USA.
Nature
|August 29, 2018
まとめ
輸出タンパク質 (PTEX) のプラズモディウムトランスロコンは構造的に明らかにされ,マラリアエフェクタータンパク質を輸出するメカニズムが明らかになった. この発見は この寄生虫の輸出システムを 標的とした薬の開発に 新たな道を開きます
科学分野:
- 構造生物学
- 寄生虫学
- 分子 機構
背景:
- エクスポートされたタンパク質のプラズモディウムトランスロコン (PTEX) 複合体は,マラリア寄生虫からのエフェクタータンパク質を宿主赤血球に輸出するために不可欠です.
- PTEXが真空膜を横切るこの転移を容易にする正確なメカニズムは,ほとんど不明である.
研究 の 目的:
- PTEXコア複合体の構造的基礎とメカニズムを解明する.
- プラズモディアム・ファルシパラムの感染時に,PTEXが効果タンパク質の輸送をどのように媒介するかを理解する.
主な方法:
- PTEXコア複合体の構造を決定するために,近原子解像度の冷凍電子顕微鏡 (cryo-EM) が使用された.
- 固有のPTEXコア複合体 (EXP2,PTEX150,HSP101) は,CRISPR- Cas9によるエピトープタグを用いてPlasmodium falciparumから分離された.
- 構造物は,貨物の移転の"関与"と"リセット"の両方でキャプチャされました.
主要な成果:
- PTEXコア複合体は,真空膜を通って静的な,フンネル状のチャンネルを形成し,互換されたEXP2とPTEX150タンパク質で構成されています.
- 螺旋状のAAA+ HSP101ヘクサマーがチャネルの上に座り,タンパク質のスレッド化を容易にするために形状の変化 (圧縮) を経験する.
- HSP101内の特定の孔のループは,貨物から分離し,後の輸出サイクルのためにトランスロコンのリセットを可能にします.
結論:
- この研究では,Plasmodium falciparumのエフェクタータンパク質が PTEXトランスロコン経由でエクスポートされる詳細なメカニズムが明らかにされています.
- 構造的な洞察は この重要な寄生虫の輸出機構を標的とした 構造に基づく薬剤設計の基盤を提供します
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