02535nas a2200229   4500008004100000022001400041245009600055210006900151260000900220300001400229490000700243520174900250653000901999653002002008653003702028653002502065653002302090100002002113700002002133700002802153856012402181       2022                        eng d  a1948-719300aSynergistic and competitive lipid interactions in the serotonin1A receptor microenvironment0 aSynergistic and competitive lipid interactions in the serotonin1  cDEC   a3403-34150 v133 a<p>
	The interaction of lipids with G-protein-coupled receptors (GPCRs) has been shown to modulate and dictate several aspects of GPCR organization and function. Diverse lipid interaction sites have been identified from structural biology, bioinformatics, and molecular dynamics studies. For example, multiple cholesterol interaction sites have been identified in the serotonin1A receptor, along with distinct and overlapping sphingolipid interaction sites. How these lipids interact with each other and what is the resultant effect on the receptor is still not clear. In this work, we have analyzed lipid-lipid crosstalk at the receptor of the serotonin1A receptor embedded in a membrane bilayer that mimics the neuronal membrane composition by long coarse-grain simulations. Using a set of similarity coefficients, we classified lipids that bind at the receptor together as synergistic cobinding, and those that bind individually as competitive. Our results show that certain lipids interact with the serotonin1A receptor in synergy with each other. Not surprisingly, the ganglioside GM1 and cholesterol show a synergistic cobinding, along with the relatively uncommon GM1-phosphatidylethanolamine (PE) and cholesterol-PE synergy. In contrast, certain lipid pairs such as cholesterol and sphingomyelin appear to be in competition at several sites, despite their coexistence in lipid nanodomains. In addition, we observed intralipid competition between two lipid tails, with the receptor exhibiting increased interactions with the unsaturated lipid tails. We believe our work represents an important step in understanding the diversity of GPCR-lipid interactions and exploring synergistic cobinding and competition in natural membranes.</p>
10aGPCR10alipid crosstalk10aMartini coarse-grain simulations10aMembrane cholesterol10aneuronal membranes1 aMohole, Madhura1 aSengupta, Durba1 aChattopadhyay, Amitabha  uhttps://library.ncl.res.in/content/synergistic-and-competitive-lipid-interactions-serotonin1a-receptor-microenvironment