ArticleBiophysical journal2014
Biophysical and molecular-dynamics studies of phosphatidic acid binding by the Dvl-2 DEP domain.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- PI(4,5)PScience signaling · 2022Article
- Selectivity of mTOR-Phosphatidic Acid Interactions Is Driven by Acyl Chain Structure and Cholesterol.Cells · 2021Article
- New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein.International journal of molecular sciences · 2020Review
- The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.The Journal of biological chemistry · 2020Article
- A small-molecule competitive inhibitor of phosphatidic acid binding by the AAA+ protein NSF/Sec18 blocks the SNARE-priming stage of vacuole fusion.The Journal of biological chemistry · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Phosphatidic acid induces conformational changes in Sec18 protomers that prevent SNARE priming.The Journal of biological chemistry · 2019Article
- The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2019Article
- Protein⁻Phospholipid Interaction Motifs: A Focus on Phosphatidic Acid.Biomolecules · 2018Review
- The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/β-Catenin Signaling in Mammalian Cells.Molecular and cellular biology · 2017Article
- Pathogenicity-associated protein domains: The fiercely-conserved evolutionary signatures.Gene reports · 2017Review
- Phosphatidic Acid Sequesters Sec18p from cis-SNARE Complexes to Inhibit Priming.Traffic (Copenhagen, Denmark) · 2016Article
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Authors and funding
9 authors.
Funding
Abstract
The Wnt-dependent, β-catenin-independent pathway modulates cell movement and behavior. A downstream regulator of this signaling pathway is Dishevelled (Dvl), which, among other multiple interactions, binds to the Frizzled receptor and the plasma membrane via phosphatidic acid (PA) in a mechanism proposed to be pH-dependent. While the Dvl DEP domain is central to the β-catenin-independent Wnt signaling function, the mechanism underlying its physical interaction with the membrane remains elusive. In this report, we elucidate the structural and functional basis of PA association to the Dvl2 DEP domain. Nuclear magnetic resonance, molecular-dynamics simulations, and mutagenesis data indicated that the domain interacted with the phospholipid through the basic helix 3 and a contiguous loop with moderate affinity. The association suggested that PA binding promoted local conformational changes in helix 2 and β-strand 4, both of which are compromised to maintain a stable hydrophobic core in the DEP domain. We also show that the Dvl2 DEP domain bound PA in a pH-dependent manner in a mechanism that resembles deprotonation of PA. Collectively, our results structurally define the PA-binding properties of the Dvl2 DEP domain, which can be exploited for the investigation of binding mechanisms of other DEP domain-interacting proteins.
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