Cryo-EM構造は,P4-ATPaseのフリッパースの輸送サイクルを捕捉する

Masahiro Hiraizumi^1,2, Keitaro Yamashita^1,3, Tomohiro Nishizawa⁴

¹Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Science (New York, N.Y.)

|August 17, 2019

まとめ

研究者は,ヒトP4-ATPasesの脂質転移サイクルを,冷凍電子顕微鏡を用いて解明した. これはこれらの重要な膜タンパク質がフォスフォリピドを輸送し細胞の非対称性を維持する方法を示しています

科学分野:

膜生物学
構造生物学
生物化学

背景:

IV型P型ATP酶 (P4-ATPases) は,真核細胞膜の脂質非対称性を維持するために不可欠である.
脂質非対称性は,膜の伝達と細胞の信号伝達に不可欠である.

研究の目的:

人間のATP8A1-CDC50a P4-ATPaseヘテロ複合体における異なる中間物質の構造を決定する.
P4-ATPasesによって媒介されるフォスフォリピド転移のメカニズムを解明する.

主な方法:

構造を得るために,冷凍電子顕微鏡 (冷凍EM) が使用された.
6つの異なる中間物質の高解像度構造 (2. 63. 3アングストーム) を決定した.

主要な成果:

この研究では,アクチュエータ領域の回転運動とトランスメブランヘリクスの横向的なシフトを含むATP依存の形状の変化が明らかになりました.
これらの構造的変化は,フォスファディチルセリンの結合と膜の横断を容易にする.
フォスフォリピドヘッド群は水性裂け目を通り,アシル鎖は脂質環境と相互作用する.

結論:

この発見は,P4-ATPaseのフリップフェーズメカニズムに関する原子レベルの洞察を提供します.
このメカニズムを理解することは,P4-ATPase変異によって引き起こされる脂質輸送および関連する疾患を理解するために不可欠です.

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