Fiche publication
Date publication
mars 2021
Journal
Proteins
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEJAEGERE Annick
Tous les auteurs :
Bianchetti L, Sinar D, Depenveiller C, Dejaegere A
Lien Pubmed
Résumé
In vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear receptor (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to the group of oxo-steroidian NRs, together with the glucocorticoid (GR), progesterone (PR), and androgen (AR) receptors. Classically, these oxo-steroidian NRs homodimerize and bind to specific genomic sequences to activate gene expression. NRs are multi-domain proteins, and dimerization is mediated by both the DNA (DBD) and ligand binding (LBD) domains, with the latter thought to provide the largest dimerization interface. However, at the structural level, the dimerization of oxo-steroidian receptors LBDs has remained largely a matter of debate and, despite their sequence homology, there is currently no consensus on a common homodimer assembly across the four receptors, that is, GR, PR, AR and MR. Here, we examined all available MR LBD crystals using different computational methods (ProtCID, PISA, PRISM, EPPIC, and the MM/PBSA method). A consensus is reached by all methods and singles out an interface mediated by helices H9, H10 and the C-terminal F domain as having characteristics of a biologically relevant assembly. Interestingly, a similar assembly was previously identified for GRα, MR closest homolog. Alternative architectures that were proposed for GRα were not observed for MR. These data call for further experimental investigations of oxo-steroid dimer architectures. This article is protected by copyright. All rights reserved.
Mots clés
F-domain, Mineralocorticoid receptor, binding free energy, glucocorticoid, homodimer, stability, structure
Référence
Proteins. 2021 Mar 12;:
