Insights into mineralocorticoid receptor homodimerization from a combined molecular modeling and bioinformatics study

In vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to group of oxo-steroidian NRs, together with glucocorticoid (GR), progesterone (PR), androgen (AR) receptors. Classically, these NRs homodimerize bind specific genomic sequences activate gene expression. are multi-domain proteins, dimerization mediated by both DNA (DBD) ligand binding domains (LBDs), latter thought provide largest interface. However, at structural level, receptors LBDs has remained largely matter debate and, despite their sequence homology, there currently no consensus on common homodimer assembly across four receptors, is, GR, PR, AR, MR. Here, we examined all available MR LBD crystals using different computational methods (protein interface database, interfaces, structures assemblies, protein-protein interaction prediction matching, evolutionary classifier, molecular mechanics Poisson-Boltzmann surface area method). A reached singles out an helices H9, H10 C-terminal F domain as having characteristics biologically relevant assembly. Interestingly, similar was previously identified for GRα, closest homolog. Alternative architectures were proposed GRα not observed These data call further experimental investigations oxo-steroid dimer architectures.