6ROH
Cryo-EM structure of the autoinhibited Drs2p-Cdc50p
Summary for 6ROH
| Entry DOI | 10.2210/pdb6roh/pdb |
| EMDB information | 4972 |
| Descriptor | Probable phospholipid-transporting ATPase DRS2, Cell division control protein 50, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total) |
| Functional Keywords | lipid flippase, lipid transport, p-type atpase, ps transport. |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) More |
| Total number of polymer chains | 2 |
| Total formula weight | 212976.60 |
| Authors | Timcenko, M.,Lyons, J.A.,Januliene, D.,Ulstrup, J.J.,Dieudonne, T.,Montigny, C.,Ash, M.R.,Karlsen, J.L.,Boesen, T.,Kuhlbrandt, W.,Lenoir, G.,Moeller, A.,Nissen, P. (deposition date: 2019-05-13, release date: 2019-07-03, Last modification date: 2024-10-09) |
| Primary citation | Timcenko, M.,Lyons, J.A.,Januliene, D.,Ulstrup, J.J.,Dieudonne, T.,Montigny, C.,Ash, M.R.,Karlsen, J.L.,Boesen, T.,Kuhlbrandt, W.,Lenoir, G.,Moeller, A.,Nissen, P. Structure and autoregulation of a P4-ATPase lipid flippase. Nature, 571:366-370, 2019 Cited by 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 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. PubMed: 31243363DOI: 10.1038/s41586-019-1344-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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