+Search query
-Structure paper
Title | Structure and autoregulation of a P4-ATPase lipid flippase. |
---|---|
Journal, issue, pages | Nature, Vol. 571, Issue 7765, Page 366-370, Year 2019 |
Publish date | Jun 26, 2019 |
Authors | 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 Abstract | 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. |
External links | Nature / PubMed:31243363 |
Methods | EM (single particle) |
Resolution | 2.8 - 3.7 Å |
Structure data | EMDB-4972, PDB-6roh: |
Chemicals | ChemComp-PSF: ChemComp-MG: ChemComp-NAG: ChemComp-HOH: ChemComp-2Y5: |
Source |
|
Keywords | LIPID TRANSPORT / Lipid Flippase / P-type ATPase / PS Transport. |