Mechanistic aspects of mineralocorticoid receptor activation
| Autor: | Chantal Hellal-Levy, Anny Souque, Marie-Edith Rafestin-Oblin, Jérôme Fagart |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Protein Folding
aldosterone medicine.drug_class ligand binding Promoter steroid receptor Biology Ligands Cell biology Transactivation antimineralocorticoid Mineralocorticoid receptor Receptors Mineralocorticoid Biochemistry Mineralocorticoid Nephrology Heat shock protein Mineralocorticoids medicine Enzyme-linked receptor Humans 5-HT5A receptor Amino Acids Receptor Mineralocorticoid Receptor Antagonists |
| Zdroj: | Kidney International. (4):1250-1255 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.2000.00958.x |
| Popis: | Mechanistic aspects of mineralocorticoid receptor activation. Aldosterone exerts its biological effects through binding to mineralocorticoid receptor (MR). Ligand binding induces a receptor transconformation within the ligand-binding domain and dissociation of associated proteins from the receptor. The ligand-activated receptor binds as a dimer to the response elements present in the promoter region of target genes and initiates the transcription through specific interactions with the transcription machinery. The glucocorticoid hormone cortisol binds to the human MR (hMR) with the same affinity as aldosterone, but is less efficient than aldosterone in stimulating the hMR transactivation. The antimineralocorticoid spirolactones also bind to the hMR but induce a receptor conformation that is transcriptionally silent. In this report, we describe the key residues involved in the recognition of agonist and antagonist ligands and propose a two-step model with a dynamic dimension for the MR activation. In its unliganded state, MR is in an opened conformation in which folding into the ligand-binding competent state requires both the heat shock protein 90 and the C-terminal part of the receptor. An intermediate complex is generated by ligand binding, leading to a more compact receptor conformation. This transient complex is then converted to a transcriptionally active conformation in which stability depends on the steroid-receptor contacts. |
| Databáze: | OpenAIRE |
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