title: 3D models of human ERα and ERβ complexed with 5-androsten-3β,17β-diol.
abstract: Recently, binding of 5-androsten-3β,17β-diol (Δ(5)-androstenediol) to human estrogen receptor-beta (ERβ) was found to repress microglia-mediated inflammation, which is associated with various neurodegenerative diseases, such as multiple sclerosis. In contrast, binding of estradiol to ERβ resulted in little or no repression of microglia-mediated inflammation. Binding of Δ(5)-androstenediol to ERβ, as well as to ERα, is unexpected because unlike estradiol, Δ(5)-androstenediol has a saturated A ring and a C19 methyl group. To begin to elucidate the interaction of Δ(5)-androstenediol with both ERs, we constructed 3D models of Δ(5)-androstenediol with human ERα and ERβ for comparison with the crystal structures of estradiol in ERα and ERβ. Conformational flexibility in human ERα and ERβ accommodates the C19 methyl on Δ(5)-androstenediol. This conformational flexibility may be relevant for binding of other Δ(5)-steroids with C19 methyl substituents, such as 25-hydroxycholesterol and 27-hydroxycholesterol, to ERs.
authors.affiliation: Department of Medicine, 0693 University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA. mbaker@ucsd.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Baker
authors.forename: Kayla Y
authors.initials: KY
authors.lastname: Uh
authors.forename: Charlie
authors.initials: C
authors.lastname: Chandsawangbhuwana
mesh_terms: D000595:Amino Acid Sequence; D015114:Androstenediol / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; D015114:Androstenediol