Structure - function relationships of the mineralcorticoid receptor

The mineralcorticoid receptor (MR) is an important therapeutic target in cardiovascular disease. We have identified interactions of the receptor that differ between the physiological hormones, aldosterone and cortisol. We also have access to novel therapeutic agents in development. Understanding these interactions and their structural basis will lead to the development of new therapeutic agents. The studies involve the use of yeast-2-hybrid screens, transactivation assays, structural analysis, mutation detection, comparative biology and a series of unique transgenic mouse models in which the MR has been either mutated or "knocked-out." This work is also associated with our clinical program. Recent publications: Structural determinants of activation of the mineralocorticoid receptor: an evolutionary perspective. Fuller PJ, Yao YZ, Yang J, Young MJ. J Hum Hypertens. 2021 Feb;35(2):110-116. doi: 10.1038/s41371-020-0360-2. Epub 2020 May 28. Molecular evolution of the switch for progesterone and spironolactone from mineralocorticoid receptor agonist to antagonist. Fuller PJ, Yao YZ, Jin R, He S, Martín-Fernández B, Young MJ, Smith BJ. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18578-18583. doi: 10.1073/pnas.1903172116. Epub 2019 Aug 22. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors. Alexander SP, Cidlowski JA, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Southan C, Davies JA, Coons L, Fuller PJ, Korach KS, Young MJ. Br J Pharmacol. 2021 Oct;178 Suppl 1:S246-S263. doi: 10.1111/bph.15540.