Lakshmanan Mangalath, Divya and Hassan Mohammed, Shabeer Ali (2021) Ligand Binding Domain of Estrogen Receptor Alpha Preserve a Conserved Structural Architecture Similar to Bacterial Taxis Receptors. Frontiers in Ecology and Evolution, 9. ISSN 2296-701X
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Abstract
It remains a mystery why estrogen hormone receptors (ERs), which are highly specific toward its endogenous hormones, are responsive to chemically distinct exogenous agents. Does it indicate that ERs are environmentally regulated? Here, we speculate that ERs would have some common structural features with prokaryotic taxis receptor responsive toward environmental signals. This study addresses the low specificity and high responsiveness of ERs toward chemically distinct exogenous substances, from an evolutionary point of view. Here, we compared the ligand binding domain (LBD) of ER alpha (α) with the LBDs of prokaryotic taxis receptors to check if LBDs share any structural similarity. Interestingly, a high degree of similarity in the domain structural fold architecture of ERα and bacterial taxis receptors was observed. The pharmacophore modeling focused on ligand molecules of both receptors suggest that these ligands share common pharmacophore features. The molecular docking studies suggest that the natural ligands of bacterial chemotaxis receptors exhibit strong interaction with human ER as well. Although phylogenetic analysis proved that these proteins are unrelated, they would have evolved independently, suggesting a possibility of convergent molecular evolution. Nevertheless, a remarkable sequence divergence was seen between these proteins even when they shared common domain structural folds and common ligand-based pharmacophore features, suggesting that the protein architecture remains conserved within the structure for a specific function irrespective of sequence identity.
Item Type: | Article |
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Subjects: | South Asian Archive > Multidisciplinary |
Depositing User: | Unnamed user with email support@southasianarchive.com |
Date Deposited: | 06 Jul 2023 04:30 |
Last Modified: | 17 May 2024 10:47 |
URI: | http://article.journalrepositoryarticle.com/id/eprint/1327 |