受体
鞘磷脂
G蛋白偶联受体
磷脂酰乙醇胺
脂质双层
鞘脂
串扰
脂质信号
脂质微区
膜脂
细胞生物学
生物
脂质代谢
化学
脂质体
生物化学
胆固醇
膜
磷脂酰胆碱
磷脂
物理
光学
作者
Madhura Mohole,Durba Sengupta,Amitabha Chattopadhyay
标识
DOI:10.1021/acschemneuro.2c00422
摘要
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.
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