6ROH

Cryo-EM structure of the autoinhibited Drs2p-Cdc50p

6ROH の概要

• エントリーDOI: 10.2210/pdb6roh/pdb
• EMDBエントリー: 4972
• 分子名称: 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)
• 機能のキーワード: lipid flippase, lipid transport, p-type atpase, ps transport.
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 212976.60

構造登録者

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. (登録日: 2019-05-13, 公開日: 2019-07-03, 最終更新日: 2024-10-09)

主引用文献

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

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: 31243363
DOI: 10.1038/s41586-019-1344-7

実験手法

ELECTRON MICROSCOPY (2.8 Å)