ArticleProceedings of the National Academy of Sciences of the United States of America2022
Design principles of PI(4,5)P
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed.
- The multifaceted significance of phosphoinositides in endocytic trafficking.FEBS letters · 2026Review
- Membrane Models and the Pursuit of Coherence.Biochemistry · 2026Review
- PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- PIPScience advances · 2025Article
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Article
- Review
- Making the cut: Multiscale simulation of membrane remodeling.Current opinion in structural biology · 2024Review
- Ion-Induced PIP2 Clustering with Martini3: Modification of Phosphate-Ion Interactions and Comparison with CHARMM36.The journal of physical chemistry. B · 2024Article
- Functional regulation of aquaporin dynamics by lipid bilayer composition.Nature communications · 2024Article
- Graph-Based Analyses of Dynamic Water-Mediated Hydrogen-Bond Networks in Phosphatidylserine: Cholesterol Membranes.Biomolecules · 2023Article
- Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging.Membranes · 2023Review
- Complexin-1 and synaptotagmin-1 compete for binding sites on membranes containing PtdInsPBiophysical journal · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Phosphatidylinositol 4,5-bisphosphate (PIP2) clustering is a key component in cell signaling, yet little is known about the atomic-level features of this phenomenon. Network-theoretic analysis of multimicrosecond atomistic simulations of PIP2 containing asymmetric bilayers under protein-free conditions, presented here, reveals how design principles of PIP2 clustering are determined by the specific cation effects. Ca2+ generates large clusters (6% are pentamer or larger) by adding existing PIP2 dimers formed by strong O‒Ca2+‒O bridging interactions of unprotonated P4/P5 phosphates. In contrast, monovalent cations (Na+ and K+) form smaller and less-stable clusters by preferentially adding PIP2 monomers. Despite having the same net charge, the affinity to P4/P5 is higher for Na+, while affinity toward glycerol P1 is higher for K+. Consequently, a mixture of K+ and Ca2+ (as would be produced by Ca2+ influx) synergistically yields larger and more stable clusters than Ca2+ alone due to the different binding preferences of these cations.
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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.