Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pippal, JB; Yao, Y; Rogerson, FM; Fuller, PJ.
Structural and functional characterization of the interdomain interaction in the mineralocorticoid receptor.
Mol Endocrinol. 2009; 23(9):1360-1370
Doi: 10.1210/me.2009-0032
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Pippal Jyotsna Brijesh
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The mineralocorticoid receptor (MR) plays a central role in electrolyte homeostasis and in cardiovascular disease. We have previously reported a ligand-dependent N/C-interaction in the MR. In the present study we sought to fully characterize the MR N/C-interaction. By using a range of natural and synthetic MR ligands in a mammalian two-hybrid assay we demonstrate that in contrast to aldosterone, which strongly induces the interaction, the physiological ligands deoxycorticosterone and cortisol weakly promote the interaction but predominantly inhibit the aldosterone-mediated N/C-interaction. Similarly, progesterone and dexamethasone antagonize the interaction. In contrast, the synthetic agonist 9alpha-fludrocortisol robustly induces the interaction. The ability of the N/C interaction to discriminate between MR agonists suggests a subtle conformational difference in the ligand-binding domain induced by these agonists. We also demonstrate that the N/C interaction is not cell specific, consistent with the evidence from a glutathione-S-transferase pull-down assay, of a direct protein-protein interaction between the N- and C-terminal domains of the MR. Examination of a panel of deletions in the N terminus suggests that several regions may be critical to the N/C-interaction. These studies have identified functional differences between physiological MR ligands, which suggest that the ligand-specific dependence of the N/C-interaction may contribute to the differential activation of the MR that has been reported in vivo.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- COS Cells -
- Cell Line -
- Cell Line, Tumor -
- Cercopithecus aethiops -
- Desoxycorticosterone - chemistry
- Glutathione Transferase - metabolism
- Humans -
- Hydrocortisone - pharmacology
- Ligands -
- Protein Conformation -
- Protein Structure, Tertiary -
- Rats -
- Receptors, Mineralocorticoid - chemistry Receptors, Mineralocorticoid - metabolism
- Swine -
- Two-Hybrid System Techniques -