ロンボイドは脂質を歪め,粘度による膜拡散の速度制限を破る

Alex J B Kreutzberger¹, Ming Ji¹, Jesse Aaron²

¹Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Room 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA.

Science (New York, N.Y.)

|February 2, 2019

まとめ

ロンボイドと呼ばれる膜内タンパク質は細胞膜で予想より速く移動します細胞の機能に不可欠なタンパク質の切断を加速します

科学分野:

膜生物学
タンパク質の生化学
セルラー信号

背景:

細胞内プロテアゼは信号伝達や宿主-病原体相互作用などの細胞プロセスに不可欠です.
これらの酵素が脂質二層の中でどのように機能するのかを理解することは重要な課題です.
酵素活性に対する膜環境の生体物理的制約は十分に理解されていません.

研究の目的:

生体細胞とモデル膜における膜内プロテアゼ,特にロムボイドの生体物理的性質と拡散ダイナミクスを調査する.
ロンボ型タンパク質が細胞膜内で効率的に機能することを可能にする分子メカニズムを解明する.
ロンボ型拡散率とその触媒活性との関係を in vivo で決定する.

主な方法:

生きたヒトとドロソフィラの細胞におけるロンボ型タンパク質と制御タンパク質の単分子可視化.
平面性脂質二層におけるタンパク質拡散の分析
脂質動力学とタンパク質の移動性に対するタンパク質-膜水性不一致の影響の評価

主要な成果:

ロンボイド内膜タンパク質は,サフマン-デルブリュック粘度限界を超える拡散率を示した.
不規則なロムボ型タンパク質の折り合いは脂質の歪みを誘発し,タンパク質の拡散を強めた.
細胞内の基質処理速度は,ロンボ型酵素の拡散率と直接相関している.

結論:

内膜タンパク質分解は,内膜内の酵素拡散によって本質的に制限されます.
ロンボ型タンパク質のユニークな構造により,膜拡散の制約を克服できます.
細胞は状の折りたたみの生体物理的特性を利用して,重要な膜内タンパク質分解の効率を高めます.

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