00696nas a2200157 4500008004100000022001400041245012700055210006900182260008000251300000800331490000800339100001800347700002000365700002400385856012900409 2014 eng d a0006-349500aPermeation of lipidated protein in bilayer using unbiased simulations reveals signature motif for protein-membrane binding0 aPermeation of lipidated protein in bilayer using unbiased simula a600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USAbBiophys SoccJAN a99A0 v1061 aThukral, Lipi1 aSengupta, Durba1 aGokhale, Rajesh, S. uhttps://library.ncl.res.in/content/permeation-lipidated-protein-bilayer-using-unbiased-simulations-reveals-signature-motif-001929nas a2200217 4500008004100000245013800041210006900179260000800248490000600256520112400262100002301386700002101409700002001430700002301450700001901473700002101492700002401513700002001537700002801557856012601585 2016 eng d00aProtein-dependent membrane interaction of a partially disordered protein complex with oleic acid : Implications for cancer lipidomics0 aProteindependent membrane interaction of a partially disordered  cOCT0 v63 a

Bovine α-lactalbumin (BLA) forms cytotoxic complexes with oleic acid (OA) that perturbs tumor cell membranes, but molecular determinants of these membrane-interactions remain poorly understood. Here, we aim to obtain molecular insights into the interaction of BLA/BLA-OA complex with model membranes. We characterized the folding state of BLA-OA complex using tryptophan fluorescence and resolved residue-specific interactions of BLA with OA using molecular dynamics simulation. We integrated membrane-binding data using a voltage-sensitive probe and molecular dynamics (MD) to demonstrate the preferential interaction of the BLA-OA complex with negatively charged membranes. We identified amino acid residues of BLA and BLA-OA complex as determinants of these membrane interactions using MD, functionally corroborated by uptake of the corresponding α-LA peptides across tumor cell membranes. The results suggest that the α-LA component of these cytotoxic complexes confers specificity for tumor cell membranes through protein interactions that are maintained even in the lipid complex, in the presence of OA.

1 aChaudhuri, Arunima1 aPrasanna, Xavier1 aAgiru, Priyanka1 aChakraborty, Hirak1 aRydstrom, Anna1 aHo, James, C. S.1 aSvanborg, Catharina1 aSengupta, Durba1 aChattopadhyay, Amitabha uhttps://library.ncl.res.in/content/protein-dependent-membrane-interaction-partially-disordered-protein-complex-oleic-acid00507nas a2200145 4500008004100000022001400041245006900055210006800124260000800192300001200200490000800212100002300220700002000243856009800263 2022 eng d a0022-263100aPreface to special issue on protein-mediated membrane remodeling0 aPreface to special issue on proteinmediated membrane remodeling cDEC a633-6350 v2551 aChakraborty, Hirak1 aSengupta, Durba uhttps://library.ncl.res.in/content/preface-special-issue-protein-mediated-membrane-remodeling01993nas 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

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.

1 aNaglekar, Amit1 aChattopadhyay, Amitabha1 aSengupta, Durba uhttps://library.ncl.res.in/content/palmitoylation-glucagon-peptide-1-receptor-modulates-cholesterol-interactions-receptor-lipid02081nas a2200241 4500008004100000022001400041245008800055210006900143260000800212300001100220490000800231520127200239653002801511653002101539653002501560653003501585653002701620100002001647700001901667700002001686700002801706856010501734 2024 eng d a0301-462200aProbing the energy landscape of the lipid interactions of the serotonin 1A receptor0 aProbing the energy landscape of the lipid interactions of the se cOCT a1072890 v3133 a

G protein-coupled receptors (GPCRs) are lipid-regulated transmembrane proteins that play a central role in cell signaling and pharmacology. Although the role of membrane lipids in GPCR function is well established, the underlying GPCR-lipid interactions have not been thermodynamically characterized due to the complexity of these interactions. In this work, we estimate the energetics and dynamics of lipid association from coarse-grain simulations of the serotonin1A receptor embedded in a complex membrane. We show that lipids bind to the receptor with varying energetics of 1-4 kT, and timescales of 1-10 mu s. The most favorable energetics and longest residence times are observed for cholesterol, glycosphingolipid GM1, phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids. Multi-exponential fitting of the contact probability suggests distinct dynamic regimes, corresponding to ps, ns and mu s timescales, that we correlate with the annular, intermediate and nonannular lipid sites. The timescales of lipid binding correspond to high barrier heights, despite their relatively weaker energetics. Our results highlight that GPCR-lipid interactions are driven by both thermodynamic interactions and the dynamical features of lipid binding.

10aGPCR-lipid interactions10aLipid energetics10aLipid residence time10aMolecular dynamics simulations10aSerotonin 1 a receptor1 aMohole, Madhura1 aNaglekar, Amit1 aSengupta, Durba1 aChattopadhyay, Amitabha uhttps://library.ncl.res.in/content/probing-energy-landscape-lipid-interactions-serotonin-1a-receptor