ArticleThe Journal of biological chemistry2013
Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Recent advances in understanding the regulatory mechanisms of P4-ATPase lipid flippases.Biochemical Society transactions · 2026Review
- Functional Characterization ofBiology · 2026Article
- Mechanistic Insights into Autoinhibition of the Human Flippase ATP8B1.The Journal of membrane biology · 2026Article
- A lipid flippase shapes the ciliary membrane and is essential for ciliogenesis.Current biology : CB · 2025Article
- The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.The Journal of cell biology · 2025Article
- Regulation of yeast polarized exocytosis by phosphoinositide lipids.Cellular and molecular life sciences : CMLS · 2024Review
- 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
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast.EMBO reports · 2023Article
- P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata.BMC microbiology · 2023Article
- Functional Analysis of the P-Type ATPases Apt2-4 fromJournal of fungi (Basel, Switzerland) · 2023Article
- The lipid flippase Drs2 regulates anterograde transport of Atg9 during autophagy.Autophagy reports · 2022Article
- Article
- Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural basis of the P4B ATPase lipid flippase activity.Nature communications · 2021Article
- Arf1 directly recruits the Pik1-Frq1 PI4K complex to regulate the final stages of Golgi maturation.Molecular biology of the cell · 2021Article
- Dynamic membranes: the multiple roles of P4 and P5 ATPases.Plant physiology · 2021Article
- Transport Pathways That Contribute to the Cellular Distribution of Phosphatidylserine.Frontiers in cell and developmental biology · 2021Review
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3 authors at 1 institution in 1 country.
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Abstract
Drs2p, a yeast type IV P-type ATPase (P4-ATPase), or flippase, couples ATP hydrolysis to phosphatidylserine translocation and the establishment of membrane asymmetry. A previous study has shown that affinity-purified Drs2p, possessing an N-terminal tandem affinity purification tag (TAPN-Drs2), retains ATPase and translocase activity, but Drs2p purified using a C-terminal tag (Drs2-TAPC) was inactive. In this study, we show that the ATPase activity of N-terminally purified Drs2p associates primarily with a proteolyzed form of Drs2p lacking the C-terminal cytosolic tail. Truncation of most of the Drs2p C-terminal tail sequence activates its ATPase activity by ∼4-fold. These observations are consistent with the hypothesis that the C-terminal tail of Drs2p is auto-inhibitory to Drs2p activity. Phosphatidylinositol 4-phosphate (PI(4)P) has been shown to positively regulate Drs2p activity in isolated Golgi membranes through interaction with the C-terminal tail. In proteoliposomes reconstituted with purified, N-terminally TAP-tagged Drs2p, both ATPase and flippase activity were significantly higher in the presence of PI(4)P. In contrast, PI(4)P had no significant effect on the activity of a truncated form of Drs2p, which lacked the C-terminal tail. This work provides the first direct evidence, in a purified system, that a phospholipid flippase is subject to auto-inhibition by its C-terminal tail, which can be relieved by a phosphoinositide to stimulate flippase activity.
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