Linked Life Data

1562546

Source:http://linkedlifedata.com/resource/pubmed/id/1562546

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-8
pubmed:dateCreated
1992-5-18
pubmed:abstractText
While the effects of the ligand (hormone) binding domain (LBD) on other receptor domain functions are known, the effects of other domains on LBD functions have not been studied. In this work, we examined the importance of the structural integrity of other domains of the human glucocorticosteroid receptor (hGR) on LBD activity (stability of 8S complexes, binding of hormone, and transformation from the 8S to the 4S form). Several mutations introduced outside the LBD affect neither the formation of stable 8S heterooligomeric complexes nor the hGR binding affinity for the agonist triamcinolone acetonide (TA) or the antagonist RU486. However, some of them led to an easier salt-induced transformation of the 8S-hGR into a 4S form. Deletion of the second zinc finger of the DNA binding domain (DBD) facilitated 8S dissociation whether the ligand was TA or RU486. Deletion of the first zinc finger facilitated dissociation only in the presence of RU486, while replacement of PRO 416 (in the N-terminal region of the DBD) by ARG destabilized the 8S form only in the presence of TA. Variations in the salt-sensitivity of the mutated 8S GR complexes as a function of the ligand suggest that the DBD may interact functionally (if not physically) with the LBD. This interaction (possibly mediated by hsp90) could be influenced by minor structural differences between agonist and antagonist-GR complexes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
727-32
pubmed:dateRevised
2006-5-1
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Mutations in the "zinc fingers" or in the N-terminal region of the DNA binding domain of the human glucocorticosteroid receptor facilitate its salt-induced transformation, but do not modify hormone binding.
pubmed:affiliation
INSERM U33, Bicêtre, France.
pubmed:publicationType
Journal Article