Effects of various estrogen ligands on the structural conformation of human estrogen receptor ?


Chen X., UZUNER U., Li M., Shi W., Yuan J. S. , Dai S. Y.

22nd World Congress on Advances in Oncology and 20th International Symposium on Molecular Medicine, Atina, Greece, 5 - 07 October 2017, pp.11-12

  • Publication Type: Conference Paper / Full Text
  • City: Atina
  • Country: Greece
  • Page Numbers: pp.11-12

Abstract

Estrogens are involved in the regulation of cardiovascular, musculoskeletal, immune and central nervous systems and play key roles during the development and maintenance of sexual and reproductive systems. Unintentional consumption of phytoestrogens and mycoestrogens coming with food or dietary supplements may mostly trigger either beneficial or adverse effects in target tissues where estrogen responses are perceived. Beyond endogenous estradiol, exterior estrogenic compounds binding to estrogen receptors (ER) with differential affinities are recognized as potential pharmaceuticals in particular for contraception and breast cancer therapy. Here we report a comparative structure dynamics information of ER ligand binding domain (LBD) interacted with eight different phytoestrogens and mycoestrogens. A comparative hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis was performed to elucidate the binding mechanism and structure dynamics changes of ER LBD upon binding with environmental estrogens including genistein, daidzein, coumestrol, quercetin, kaempferol, fisetin, resveratrol and zearalenone. The cluster analysis based on the HDX-MS assay data revealed a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. The obtained data further highlight that structure dynamics could be a useful strategy to elucidate the structure function relationships when endocrine disrupters interact with estrogen receptors.