Evidence map›Paper›PMID 31243363›Full record

ArticleNature2019

Structure and autoregulation of a P4-ATPase lipid flippase.

Milena Timcenko, Joseph A Lyons, Dovile Januliene, Jakob J Ulstrup, Thibaud Dieudonné, Cédric Montigny, Miriam-Rose Ash, Jesper Lykkegaard Karlsen, Thomas Boesen, Werner Kühlbrandt and 3 more

Open access · goldAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
8.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 174 citations in OpenAlex.

  1. Review
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  10. Conduction pathway for potassium through the E. coli pump KdpFABC.bioRxiv : the preprint server for biology · 2025
    Article
  11. Flippase-Mediated Hybrid Vesicle Division.Advanced materials (Deerfield Beach, Fla.) · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 3 countries.

Milena Timcenko *DANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Joseph A Lyons *DANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Dovile Januliene *Max Planck Institute for Biophysics, Frankfurt, Germany.
Jakob J UlstrupDANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Thibaud DieudonnéInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Cédric MontignyInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Miriam-Rose AshDANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Jesper Lykkegaard KarlsenDANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Thomas BoesenDANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Werner KühlbrandtMax Planck Institute for Biophysics, Frankfurt, Germany.
Guillaume LenoirInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France. guillaume.lenoir@i2bc.paris-saclay.fr.
Arne MoellerMax Planck Institute for Biophysics, Frankfurt, Germany. arne.moeller@biophys.mpg.de.
Poul NissenDANDRITE, Nordic EMBL Partnership for Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark. pn@mbg.au.dk.
Aarhus University · DKMax Planck Institute of Biophysics · DECommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRDanish National Research Foundation · DKInstitut de Biologie Intégrative de la Cellule · FRLaboratoire de Biologie Physico-Chimique des Protéines Membranaires · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Cryoelectron MicroscopyBinding SitesBiological TransportCalcium-Transporting ATPasesEnzyme ActivationLipid BilayersModels, BiologicalModels, MolecularPhosphatidylethanolaminesPhosphatidylinositol PhosphatesPhosphatidylserinesProtein DomainsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCalcium-Transporting ATPasesCDC50 protein, S cerevisiaeDRS2 protein, S cerevisiaeLipid BilayersphosphatidylethanolaminePhosphatidylethanolaminesphosphatidylinositol 4-phosphatePhosphatidylinositol PhosphatesPhosphatidylserinesSaccharomyces cerevisiae Proteins

Identifiers

PMID31243363
OpenAlexW2953771712

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.