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Species differences in ligand interaction and activation of estrogen receptors in fish and human
Örebro universitet, Institutionen för naturvetenskap och teknik. (Biology, The Life Science Center)
Örebro universitet, Institutionen för naturvetenskap och teknik. (Biology, The Life Science Center)
Örebro universitet, Institutionen för naturvetenskap och teknik. (Biology, The Life Science Center)ORCID-id: 0000-0001-7336-6335
2019 (Engelska)Ingår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, artikel-id 105450Artikel i tidskrift (Refereegranskat) Epub ahead of print
Abstract [en]

Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (β) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERβ and seabream ERβ2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.

Ort, förlag, år, upplaga, sidor
Pergamon Press, 2019. artikel-id 105450
Nyckelord [en]
In silico, ligand binding pocket, ligand resolution, ligand specificity, species-specific
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:oru:diva-75906DOI: 10.1016/j.jsbmb.2019.105450PubMedID: 31437548OAI: oai:DiVA.org:oru-75906DiVA, id: diva2:1349544
Tillgänglig från: 2019-09-09 Skapad: 2019-09-09 Senast uppdaterad: 2019-09-09Bibliografiskt granskad

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Asnake, SolomonModig, CarinaOlsson, Per-Erik

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