02311nas a2200241   4500008004100000022001400041245008800055210006900143260000800212300001100220490000800231520148500239653001601724653001801740653003901758653003101797653003001828100002501858700002401883700002601907700002001933856011601953       2020                        eng d  a0009-308400aLipid-dependent conformational landscape of the ErbB2 growth factor receptor dimers0 aLipiddependent conformational landscape of the ErbB2 growth fact  cAUG  a1049110 v2303 a<p>Altered lipid metabolism has been linked to cancer development and progression. Several roles have been attributed to the increased saturation and length of lipid acyl tails observed in tumors, but its effect on signaling receptors is still emerging. In this work, we have analyzed the lipid dependence of the ErbB2 growth factor receptor dimerization that plays an important role in the pathogenesis of breast cancer. We have performed coarse-grain ensemble molecular dynamics simulations to comprehensively sample the ErbB2 monomer-dimer association. Our results indicate a dynamic dimer state with a complex conformational landscape that is modulated with increasing lipid tail length. We resolve the native N-terminal ``active'' and C-terminal ``inactive'' conformations in all membrane compositions. However, the relative population of the N-terminal and C-terminal conformers is dependent on length of the saturated lipid tails. In short-tail membranes, additional non-specific dimers are observed which are reduced or absent in long-tailed bilayers. Our results indicate that the relative population as well as the structure of the dimer state is modulated by membrane composition. We have correlated these differences to local perturbations of the membrane around the receptor. Our work is an important step in characterizing ErbB dimers in healthy and diseased states and emphasize the importance of sampling lipid dynamics in understanding receptor association.</p>
10aErbB2 dimer10aLipid effects10aMartini coarse-grained simulations10aMembrane protein structure10aTransmembrane association1 aGopal, Srinivasa, M.1 aPawar, Aiswarya, B.1 aWassenaar, Tsjerk, A.1 aSengupta, Durba  uhttps://library.ncl.res.in/content/lipid-dependent-conformational-landscape-erbb2-growth-factor-receptor-dimers