Glucocorticoid receptor complexes form cooperatively with the Hsp90 co-chaperones Pp5 and FKBPs.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
11
02
2020
accepted:
29
05
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The function of steroid receptors in the cell depends on the chaperone machinery of Hsp90, as Hsp90 primes steroid receptors for hormone binding and transcriptional activation. Several conserved proteins are known to additionally participate in receptor chaperone assemblies, but the regulation of the process is not understood in detail. Also, it is unknown to what extent the contribution of these cofactors is conserved in other eukaryotes. We here examine the reconstituted C. elegans and human chaperone assemblies. We find that the nematode phosphatase PPH-5 and the prolyl isomerase FKB-6 facilitate the formation of glucocorticoid receptor (GR) complexes with Hsp90. Within these complexes, Hsp90 can perform its closing reaction more efficiently. By combining chemical crosslinking and mass spectrometry, we define contact sites within these assemblies. Compared to the nematode Hsp90 system, the human system shows less cooperative client interaction and a stricter requirement for the co-chaperone p23 to complete the closing reaction of GR·Hsp90·Pp5/Fkbp51/Fkbp52 complexes. In both systems, hormone binding to GR is accelerated by Hsp90 alone and in the presence of its cofactors. Our results show that cooperative complex formation and hormone binding patterns are, in many aspects, conserved between the nematode and human systems.
Identifiants
pubmed: 32612187
doi: 10.1038/s41598-020-67645-8
pii: 10.1038/s41598-020-67645-8
pmc: PMC7329908
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Glycoproteins
0
HSP90 Heat-Shock Proteins
0
Receptors, Glucocorticoid
0
tissue-factor-pathway inhibitor 2
0
Tacrolimus Binding Proteins
EC 5.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10733Références
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