Matches in SemOpenAlex for { <https://semopenalex.org/work/W2801409401> ?p ?o ?g. }
- W2801409401 endingPage "1825" @default.
- W2801409401 startingPage "1810" @default.
- W2801409401 abstract "Nuclear hormone receptors (NRs) constitute a large family of multi-domain ligand-activated transcription factors. Dimerization is essential for their regulation, and both DNA binding domain (DBD) and ligand binding domain (LBD) are implicated in dimerization. Intriguingly, the glucocorticoid receptor-α (GRα) presents a DBD dimeric architecture similar to that of the homologous estrogen receptor-α (ERα), but an atypical dimeric architecture for the LBD. The physiological relevance of the proposed GRα LBD dimer is a subject of debate.We analyzed all GRα LBD homodimers observed in crystals using an energetic analysis based on the PISA and on the MM/PBSA methods and a sequence conservation analysis, using the ERα LBD dimer as a reference point.Several dimeric assemblies were observed for GRα LBD. The assembly generally taken to be physiologically relevant showed weak binding free energy and no significant residue conservation at the contact interface, while an alternative homodimer mediated by both helix 9 and C-terminal residues showed significant binding free energy and residue conservation. However, none of the GRα LBD assemblies found in crystals are as stable or conserved as the canonical ERα LBD dimer. GRα C-terminal sequence (F-domain) forms a steric obstacle to the canonical dimer assembly in all available structures.Our analysis calls for a re-examination of the currently accepted GRα homodimer structure and experimental investigations of the alternative architectures.This work questions the validity of the currently accepted architecture. This has implications for interpreting physiological data and for therapeutic design pertaining to glucocorticoid research." @default.
- W2801409401 created "2018-05-17" @default.
- W2801409401 creator A5005345147 @default.
- W2801409401 creator A5005950099 @default.
- W2801409401 creator A5039743286 @default.
- W2801409401 creator A5040778539 @default.
- W2801409401 creator A5043614893 @default.
- W2801409401 creator A5047743339 @default.
- W2801409401 creator A5080072024 @default.
- W2801409401 date "2018-08-01" @default.
- W2801409401 modified "2023-10-14" @default.
- W2801409401 title "Alternative dimerization interfaces in the glucocorticoid receptor-α ligand binding domain" @default.
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