ArticleNature communications2019
Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Recent advances in understanding the regulatory mechanisms of P4-ATPase lipid flippases.Biochemical Society transactions · 2026Review
- Functional Characterization ofBiology · 2026Article
- Evolutionary Prevalence of the Electrostatic Switch Mechanism in P-type ATPases.The Journal of membrane biology · 2026Article
- A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis.Current biology : CB · 2025Article
- P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance.Nature cell biology · 2025Article
- The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.The Journal of cell biology · 2025Article
- P4-ATPase control over phosphoinositide membrane asymmetry and neomycin resistance.bioRxiv : the preprint server for biology · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.Archives of biochemistry and biophysics · 2024Article
- Consensus, controversies, and conundrums of P4-ATPases: The emerging face of eukaryotic lipid flippases.The Journal of biological chemistry · 2024Review
- Dopey-dependent regulation of extracellular vesicles maintains neuronal morphology.bioRxiv : the preprint server for biology · 2024Article
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases.Nature reviews. Molecular cell biology · 2023Review
- The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast.EMBO reports · 2023Article
- Functional Analysis of the P-Type ATPases Apt2-4 fromJournal of fungi (Basel, Switzerland) · 2023Article
- Apically-located P4-ATPase1-Lem1 complex internalizes phosphatidylserine and regulates motility-dependent invasion and egress inComputational and structural biotechnology journal · 2023Article
- Lipid Transport byInfection and immunity · 2022Article
- Yeast as a tool for membrane protein production and structure determination.FEMS yeast research · 2022Article
- In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites.Membranes · 2022Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry. The enzyme complex exists in an autoinhibited form in the absence of an activator and is specifically activated by phosphatidylinositol-4-phosphate (PI4P), although the underlying mechanisms have been unclear. Here we report the cryo-EM structures of intact Drs2p-Cdc50p isolated from S. cerevisiae in apo form and in the PI4P-activated form at 2.8 Å and 3.3 Å resolution, respectively. The structures reveal that the Drs2p C-terminus lines a long groove in the cytosolic regulatory region to inhibit the flippase activity. PIP4 binding in a cytosol-proximal membrane region triggers a 90° rotation of a cytosolic helix switch that is located just upstream of the inhibitory C-terminal peptide. The rotation of the helix switch dislodges the C-terminus from the regulatory region, activating the flippase.
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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.