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-Structure paper
タイトル | Structure and autoregulation of a P4-ATPase lipid flippase. |
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ジャーナル・号・ページ | Nature, Vol. 571, Issue 7765, Page 366-370, Year 2019 |
掲載日 | 2019年6月26日 |
著者 | Milena Timcenko / Joseph A Lyons / Dovile Januliene / Jakob J Ulstrup / Thibaud Dieudonné / Cédric Montigny / Miriam-Rose Ash / Jesper Lykkegaard Karlsen / Thomas Boesen / Werner Kühlbrandt / Guillaume Lenoir / Arne Moeller / Poul Nissen / |
PubMed 要旨 | Type 4 P-type ATPases (P4-ATPases) are lipid flippases that drive the active transport of phospholipids from exoplasmic or luminal leaflets to cytosolic leaflets of eukaryotic membranes. The ...Type 4 P-type ATPases (P4-ATPases) are lipid flippases that drive the active transport of phospholipids from exoplasmic or luminal leaflets to cytosolic leaflets of eukaryotic membranes. The molecular architecture of P4-ATPases and the mechanism through which they recognize and transport lipids have remained unknown. Here we describe the cryo-electron microscopy structure of the P4-ATPase Drs2p-Cdc50p, a Saccharomyces cerevisiae lipid flippase that is specific to phosphatidylserine and phosphatidylethanolamine. Drs2p-Cdc50p is autoinhibited by the C-terminal tail of Drs2p, and activated by the lipid phosphatidylinositol-4-phosphate (PtdIns4P or PI4P). We present three structures that represent the complex in an autoinhibited, an intermediate and a fully activated state. The analysis highlights specific features of P4-ATPases and reveals sites of autoinhibition and PI4P-dependent activation. We also observe a putative lipid translocation pathway in this flippase that involves a conserved PISL motif in transmembrane segment 4 and polar residues of transmembrane segments 2 and 5, in particular Lys1018, in the centre of the lipid bilayer. |
リンク | Nature / PubMed:31243363 |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.7 Å |
構造データ | |
化合物 | ChemComp-PSF: ChemComp-MG: ChemComp-NAG: ChemComp-HOH: ChemComp-2Y5: |
由来 |
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キーワード | LIPID TRANSPORT / Lipid Flippase / P-type ATPase / PS Transport. |