02054nas a2200205   4500008004100000022001400041245009000055210006900145260000800214520132800222653001601550653003301566653001501599653002401614653003701638653001701675100002401692700002001716856011201736       2021                        eng d  a0022-263100aRole of cholesterol in transmembrane dimerization of the ErbB2 growth factor receptor0 aRole of cholesterol in transmembrane dimerization of the ErbB2 g  cJAN3 a<p>The association of ErbB2 growth factor receptors is critical for cell growth and potentiates tumor proliferation in several cancer types. An important aspect in ErbB2 association is the role of lipids such as cholesterol, especially since their metabolism is often reprogrammed in cancer cells. Here, we have coupled metadynamics with coarse-grain simulations to identify cholesterol effects in the transmembrane dimerization of ErbB2 receptors. Overall, cholesterol interactions are observed with the receptor that directly tunes the association energetics. Several dimer conformations are identified both in the presence and absence of cholesterol, although the dimer regime appears to be more favorable in the presence of cholesterol. We observe an overall modulation of the underlying energy profile and the symmetric active and inactive conformational states are not distinguished in the presence of cholesterol. We show that cholesterol binds to the receptor transmembrane domain at a site (CRAC motif) that overlaps with the dimer interface (SmXXXSm motif). The competition between the transmembrane interactions and cholesterol interactions decides the final conformational landscape. Our work is an important step toward characterizing cholesterol effects in ErbB2 membrane receptor function. [GRAPHICS] .</p>
10aCholesterol10aErbB2 growth factor receptor10aHer2 dimer10aJuxtamembrane dimer10aMartini coarse-grain simulations10aMetadynamics1 aPawar, Aiswarya, B.1 aSengupta, Durba  uhttps://library.ncl.res.in/content/role-cholesterol-transmembrane-dimerization-erbb2-growth-factor-receptor02535nas 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-microenvironment01829nas a2200217   4500008004100000022001400041245009100055210006900146260000900215490000700224520105300231653002101284653002101305653003701326653003501363653003101398100002001429700002001449700002001469856012201489       2023                        eng d  a1439-423500aCofilin-membrane interactions: electrostatic effects in phosphoinositide lipid binding0 aCofilinmembrane interactions electrostatic effects in phosphoino  cFEB 0 v243 a<p>
	The actin cytoskeleton interacts with the cell membrane primarily through the indirect interactions of actin-binding proteins such as cofilin-1. The molecular mechanisms underlying the specific interactions of cofilin-1 with membrane lipids are still unclear. Here, we performed coarse-grain molecular dynamics simulations of cofilin-1 with complex lipid bilayers to analyze the specificity of protein-lipid interactions. We observed the maximal interactions with phosphoinositide (PIP) lipids, especially PIP2 and PIP3 lipids. A good match was observed between the residues predicted to interact and previous experimental studies. The clustering of PIP lipids around the membrane bound protein leads to an overall lipid demixing and gives rise to persistent membrane curvature. Further, through a series of control simulations, we observe that both electrostatics and geometry are critical for specificity of lipid binding. Our current study is a step towards understanding the physico-chemical basis of cofilin-PIP lipid interactions.</p>
10acomplex membrane10alipid clustering10aMartini coarse-grain simulations10aMolecular dynamics simulations10aProtein-lipid interactions1 aPrakash, Shikha1 aKrishna, Anjali1 aSengupta, Durba  uhttps://library.ncl.res.in/content/cofilin-membrane-interactions-electrostatic-effects-phosphoinositide-lipid-binding