Nanodomains enriched in arachidonic acid promote P2Y12 receptor oligomerization in the platelet plasma membrane
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
39557210
DOI
10.1016/j.bbamem.2024.184402
PII: S0005-2736(24)00133-0
Knihovny.cz E-resources
- Keywords
- Arachidonic acid, Blood platelets, Molecular dynamics simulation, Protein Multimerization, Protein–lipid interaction, Purinergic receptor P2Y12,
- MeSH
- Cell Membrane * metabolism chemistry MeSH
- Cholesterol metabolism chemistry MeSH
- Arachidonic Acid * metabolism chemistry MeSH
- Humans MeSH
- Protein Multimerization MeSH
- Receptors, Purinergic P2Y12 * metabolism chemistry MeSH
- Molecular Dynamics Simulation * MeSH
- Blood Platelets * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cholesterol MeSH
- Arachidonic Acid * MeSH
- P2RY12 protein, human MeSH Browser
- Receptors, Purinergic P2Y12 * MeSH
P2Y12 receptors on the platelet plasma membrane are targeted by several antiplatelets drugs. Although oligomerization and functioning of P2Y12 receptors depend on the membrane environment, little is known about their preferred membrane localization and the role of surrounding lipid composition, especially the arachidonic acids (ARA), which are abundant in platelets. Coarse-grained molecular dynamics simulations of platelet plasma membrane based on the lipidomics data were used to investigate the P2Y12 lipid environment and the involvement of ARA in its oligomerization in platelet plasma membranes. The platelet plasma membrane contains two types of lipids nanodomains: ordered, enriched in SM and cholesterol, and disordered, enriched in ARA-containing lipids. P2Y12 receptors prefer to localize in these ARA-rich domains and induce the sorting of the ARA-containing lipids in their vicinity. This ARA-rich environment promotes the oligomerization of P2Y12 receptors and stabilizes the protein-protein interfaces of oligomers. As summary, oligomerization of P2Y12 receptors is promoted in ARA-rich nano-domains of the platelet plasma membrane.
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