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-receptor