ArticleJournal of the American Chemical Society2015
Quantifying transient interactions between Bacillus phosphatidylinositol-specific phospholipase-C and phosphatidylcholine-rich vesicles.
Article in Journal of the American Chemical Society, 2015. 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, 25 citations in OpenAlex.
- Thermostable Esterase from ThermophilicGenes · 2025Article
- The Martini 3 Lipidome: Expanded and Refined Parameters Improve Lipid Phase Behavior.ACS central science · 2025Article
- Standard Binding Free Energy and Membrane Desorption Mechanism for a Phospholipase C.Journal of chemical information and modeling · 2022Article
- Dissecting peripheral protein-membrane interfaces.PLoS computational biology · 2022Article
- Phosphatidylcholine Cation-Tyrosine π Complexes: Motifs for Membrane Binding by a Bacterial Phospholipase C.Molecules (Basel, Switzerland) · 2022Review
- Regulation of bifunctional proteins in cells: Lessons from the phospholipase Cβ/G protein pathway.Protein science : a publication of the Protein Society · 2020Review
- Capturing Choline-Aromatics Cation-π Interactions in the MARTINI Force Field.Journal of chemical theory and computation · 2020Article
- Defining the subcellular distribution and metabolic channeling of phosphatidylinositol.The Journal of cell biology · 2020Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- A model for hydrophobic protrusions on peripheral membrane proteins.PLoS computational biology · 2018Article
- Atomic-level description of protein-lipid interactions using an accelerated membrane model.Biochimica et biophysica acta · 2016Review
- A Role for Weak Electrostatic Interactions in Peripheral Membrane Protein Binding.Biophysical journal · 2016Article
- Fluorinated Aromatic Amino Acids Distinguish Cation-π Interactions from Membrane Insertion.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Bacillus thuringiensis secretes the virulence factor phosphatidylinositol-specific phospholipase C (BtPI-PLC), which specifically binds to phosphatidylcholine (PC) and cleaves GPI-anchored proteins off eukaryotic plasma membranes. To elucidate how BtPI-PLC searches for GPI-anchored proteins on the membrane surface, we measured residence times of single fluorescently labeled proteins on PC-rich small unilamellar vesicles (SUVs). BtPI-PLC interactions with the SUV surface are transient with a lifetime of 379 ± 49 ms. These data also suggest that BtPI-PLC does not directly sense curvature, but rather prefers to bind to the numerous lipid packing defects in SUVs. Despite this preference for defects, all-atom molecular dynamics simulations of BtPI-PLC interacting with PC-rich bilayers show that the protein is shallowly anchored with the deepest insertions ∼18 Å above the bilayer center. Membrane partitioning is mediated, on average, by 41 hydrophobic, 8 hydrogen-bonding, and 2 cation-π (between PC choline headgroups and Tyr residues) transient interactions with phospholipids. These results lead to a quantitative model for BtPI-PLC interactions with cell membranes where protein binding is mediated by lipid packing defects, possibly near GPI-anchored proteins, and the protein diffuses on the membrane for ∼100-380 ms, during which time it may cleave ∼10 GPI-anchored proteins before dissociating. This combination of short two-dimensional scoots followed by three-dimensional hops may be an efficient search strategy on two-dimensional surfaces with obstacles.
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Registered trials
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.