Characterization of evolutionary trend in squamate estrogen receptor sensitivity
| Autor: | Satomi Kohno, Yoshinao Katsu, Louis J. Guillette, Yasuhiko Ohta, Ryohei Yatsu, Johannes H. van Wyk, Taisen Iguchi, Yukiko Ogino, Shinichi Miyagawa, Takeshi Mizutani, Jan G. Myburgh |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine medicine.medical_specialty Transcription Genetic medicine.drug_class In silico Protein domain Estrogen receptor Biology Ligands 03 medical and health sciences Endocrinology Protein Domains Internal medicine medicine Animals Estrogen Receptor beta Computer Simulation Amino Acid Sequence Cloning Molecular Estrogen receptor beta Reporter gene Estrogen Receptor alpha Lizards Biological Evolution Cell biology 030104 developmental biology Receptors Estrogen Nuclear receptor Estrogen Animal Science and Zoology Estrogen receptor alpha |
| Zdroj: | General and Comparative Endocrinology. 238:88-95 |
| ISSN: | 0016-6480 |
| DOI: | 10.1016/j.ygcen.2016.04.005 |
| Popis: | Steroid hormones are a key regulator of reproductive biology in vertebrates, and are largely regulated via nuclear receptor families. Estrogen signaling is regulated by two estrogen receptor (ER) subtypes alpha and beta in the nucleus. In order to understand the role of estrogen in vertebrates, these ER from various species have been isolated and were functionally analyzed using luciferase reporter gene assays. Interestingly, species difference in estrogen sensitivity has been noted in the past, and it was reported that snake ER displayed highest estrogen sensitivity. Here, we isolated additional ER from three lizards: chameleon (Bradypodion pumilum), skink (Plestiodon finitimus), and gecko (Gekko japonicus). We have performed functional characterization of these ERs using reporter gene assay system, and found high estrogen sensitivity in all three species. Furthermore, comparison with results from other tetrapod ER revealed a seemingly uniform gradual pattern of ligand sensitivity evolution. In silico 3D homology modeling of the ligand-binding domain revealed structural variation at three sites, helix 2, and juncture between helices 8 and 9, and caudal region of helix 10/11. Docking simulations indicated that predicted ligand-receptor interaction also correlated with the reporter assay results, and overall squamates displayed highest stabilized interactions. The assay system and homology modeling system provides tool for in-depth comparative analysis of estrogen function, and provides insight toward the evolution of ER among vertebrates. |
| Databáze: | OpenAIRE |
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