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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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.