5toa | pdb_00005toa

Crystal Structure of ER beta bound to Estradiol

spinqualitylabelsall models 5toa, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5toa is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EST Gene: ESR2, ESTRB, NR3A2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ESR2_HUMAN] Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual. Publication Abstract from PubMed The natural ligand 17beta-estradiol (E2) is so far believed to induce a unique agonist-bound active conformation in the ligand binding domain (LBD) of the estrogen receptors (ERs). Both subtypes, ERalpha and ERbeta, are transcriptionally activated in the presence of E2 with ERbeta being somewhat less active than ERalpha under similar conditions. The molecular bases for this intriguing behavior are mainly attributed to subtype differences in the amino-terminal domain of these receptors. However, structural details that confer differences in the molecular response of ER LBDs to E2 still remain elusive. In this study, we present a new crystallographic structure of the ERbeta LBD bound to E2 in which H12 assumes an alternative conformation that resembles antagonist ERs structures. Structural observations and molecular dynamics simulations jointly provide evidence that alternative ERbeta H12 position could correspond to a stable conformation of the receptor under physiological pH conditions. Our findings shed light on the unexpected role of LBD in the lower functional response of ERbeta subtype. An alternative conformation of ERbeta bound to estradiol reveals H12 in a stable antagonist position.,Souza PCT, Textor LC, Melo DC, Nascimento AS, Skaf MS, Polikarpov I Sci Rep. 2017 Jun 14;7(1):3509. doi: 10.1038/s41598-017-03774-x. PMID:28615710 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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