@article { ISI:000337000400508, title = {Permeation of lipidated protein in bilayer using unbiased simulations reveals signature motif for protein-membrane binding}, journal = {Biophysical Journal}, volume = {106}, number = {2, 1}, year = {2014}, note = {58th Annual Meeting of the Biophysical-Society, San Francisco, CA, FEB 15-19, 2014}, month = {JAN}, pages = {99A}, publisher = {Biophys Soc}, address = {600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA}, issn = {0006-3495}, author = {Thukral, Lipi and Sengupta, Durba and Gokhale, Rajesh S.} } @article {42993, title = {Protein-dependent membrane interaction of a partially disordered protein complex with oleic acid : Implications for cancer lipidomics}, journal = {Scientific Reports}, volume = {6}, year = {2016}, month = {OCT}, abstract = {

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.

}, doi = {10.1038/srep35015}, author = {Chaudhuri, Arunima and Prasanna, Xavier and Agiru, Priyanka and Chakraborty, Hirak and Rydstrom, Anna and Ho, James C. S. and Svanborg, Catharina and Sengupta, Durba and Chattopadhyay, Amitabha} } @article {48360, title = {Preface to special issue on protein-mediated membrane remodeling}, journal = {Journal of Membrane Biology}, volume = {255}, year = {2022}, month = {DEC}, pages = {633-635}, type = {Editorial Material}, issn = {0022-2631}, doi = {10.1007/s00232-022-00273-7}, author = {Chakraborty, Hirak and Sengupta, Durba} } @article {48968, title = {Palmitoylation of the glucagon-like peptide-1 receptor modulates cholesterol interactions at the receptor-lipid microenvironment}, journal = {Journal of Physical Chemistry B}, volume = {127}, year = {2023}, month = {DEC }, pages = {11000-11010}, type = {Article}, abstract = {

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.

}, issn = {1520-6106}, doi = {10.1021/acs.jpcb.3c05930}, author = {Naglekar, Amit and Chattopadhyay, Amitabha and Sengupta, Durba} } @article {49361, title = {Probing the energy landscape of the lipid interactions of the serotonin 1A receptor}, journal = {Biophysical Chemistry}, volume = {313}, year = {2024}, month = {OCT}, pages = {107289}, type = {Article}, abstract = {

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.

}, keywords = {GPCR-lipid interactions, Lipid energetics, Lipid residence time, Molecular dynamics simulations, Serotonin 1 a receptor}, issn = {0301-4622}, doi = {10.1016/j.bpc.2024.107289}, author = {Mohole, Madhura and Naglekar, Amit and Sengupta, Durba and Chattopadhyay, Amitabha} }