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.

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences CZ 166 10 Prague Czech Republic; Receptor AI Inc 20 22 Wenlock Road London N1 7GU United Kingdom; Department of Physical Chemistry Faculty of Science Palacký University Olomouc 17 listopadu 12 771 46 Olomouc Czech Republic; Department of Physics of Biological Systems Institute of Physics of the National Academy of Sciences of Ukraine Prospect Nauky 46 03028 Kyiv Ukraine

Université de Franche Comté CHU Besançon SINERGIES Service de Pharmacologie Clinique et Toxicologie F 25000 Besançon France

Université de Franche Comté CNRS Chrono environnement F 25000 Besançon France

Université de Franche Comté SINERGIES F 25000 Besançon France; Université de Franche Comté CNRS Chrono environnement F 25000 Besançon France

Citace poskytuje Crossref.org