Journal
STEROIDS
Volume 76, Issue 13, Pages 1451-1457Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2011.07.015
Keywords
Lamprey corticoid receptor; Corticosteroid receptor evolution; 11-Deoxycortisol; Helix 3-helix 5 contact
Ask authors/readers for more resources
The serum of Atlantic sea lamprey, a basal vertebrate, contains two corticosteroids, 11-deoxycortisol and deoxycorticosterone. Only 11-deoxycortisol has high affinity [K(d) similar to 3 nM] for the corticoid receptor [CR] in lamprey gill cytosol. To investigate the binding of 11-deoxycortisol to the CR, we constructed 3D models of lamprey CR complexed with 11-deoxycortisol and deoxycorticosterone. These 3D models reveal that Leu-220 and Met-299 in lamprey CR have contacts with the 17 alpha-hydroxyl on 11-deoxycortisol. Lamprey CR is the ancestor of the mineralocorticoid receptor [MR] and glucocorticoid receptor [GR]. Unlike human MR and human GR, the 3D model of lamprey CR finds a van der Waals contact between Cys-227 in helix 3 and Met-264 in helix 5. Mutant human MR and GR containing a van der Waals contact between helix 3 and helix 5 display enhanced responses to progesterone and glucocorticoids, respectively. We propose that this interaction was present in the CR and lost during the evolution of the MR and GR, leading to changes in their response to progesterone and corticosteroids, respectively. (C) 2011 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available