01993nas a2200169   4500008004100000022001400041245013300055210006900188260000900257300001600266490000800282520133400290100001901624700002801643700002001671856013201691       2023                        eng d  a1520-610600aPalmitoylation of the glucagon-like peptide-1 receptor modulates cholesterol interactions at the receptor-lipid microenvironment0 aPalmitoylation of the glucagonlike peptide1 receptor modulates c  cDEC   a11000-110100 v1273 a<p>
	The G protein-coupled receptor (GPCR) superfamily of cell surface receptors has been shown to be functionally modulated by post-translational modifications. The glucagon-like peptide receptor-1 (GLP-1R), which is a drug target in diabetes and obesity, undergoes agonist-dependent palmitoyl tail conjugation. The palmitoylation in the C-terminal domain of GLP-1R has been suggested to modulate the receptor-lipid microenvironment. In this work, we have performed coarse-grain molecular dynamics simulations of palmitoylated and nonpalmitoylated GLP-1R to analyze the differential receptor-lipid interactions. Interestingly, the placement and dynamics of the C-terminal domain of GLP-1R are found to be directly dependent on the palmitoyl tail. We observe that both cholesterol and phospholipids interact with the receptor but display differential interactions in the presence and absence of the palmitoyl tail. We characterize important cholesterol-binding sites and validate sites that have been previously reported in experimentally resolved structures of the receptor. We show that the receptor acts like a conduit for cholesterol flip-flop by stabilizing cholesterol in the membrane core. Taken together, our work represents an important step in understanding the molecular effects of lipid modifications in GPCRs.</p>
1 aNaglekar, Amit1 aChattopadhyay, Amitabha1 aSengupta, Durba  uhttps://library.ncl.res.in/content/palmitoylation-glucagon-peptide-1-receptor-modulates-cholesterol-interactions-receptor-lipid