Glucocorticoid resistance conferring mutation in the C-terminus of GR alters the receptor conformational dynamics.
Sci Rep
; 11(1): 12515, 2021 06 15.
Article
de En
| MEDLINE
| ID: mdl-34131228
ABSTRACT
The glucocorticoid receptor is a key regulator of essential physiological processes, which under the control of the Hsp90 chaperone machinery, binds to steroid hormones and steroid-like molecules and in a rather complicated and elusive response, regulates a set of glucocorticoid responsive genes. We here examine a human glucocorticoid receptor variant, harboring a point mutation in the last C-terminal residues, L773P, that was associated to Primary Generalized Glucocorticoid Resistance, a condition originating from decreased affinity to hormone, impairing one or multiple aspects of GR action. Using in vitro and in silico methods, we assign the conformational consequences of this mutation to particular GR elements and report on the altered receptor properties regarding its binding to dexamethasone, a NCOA-2 coactivator-derived peptide, DNA, and importantly, its interaction with the chaperone machinery of Hsp90.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Récepteurs aux glucocorticoïdes
/
Protéines du choc thermique HSP90
/
Glucocorticoïdes
/
Conformation moléculaire
Limites:
Animals
/
Humans
Langue:
En
Journal:
Sci Rep
Année:
2021
Type de document:
Article
Pays d'affiliation:
Allemagne