Identification of protein contact sites within the glucocorticoid/progestin response element

Carol Cairns, Jan Åke Gustafsson, Jan Carlstedt-Duke

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The glucocorticoid receptor (GR) and the progestin receptor (PR) bind specifically to a variety of DNA sequences, glucocorticoid/progestin response elements (GRE/PRE), located in the proximity of responsive gene promoters. Using the isolated recombinant GR DNA-binding domain (DBD), it has recently been shown that GR interacts with the GRE/PRE, a 15-basepair partially palindromic consensus sequence, as a dimer. In this study an investigation into the GR-GRE/PRE and PR-GRE/PRE interaction has been performed using missing base contact analysis with the tyrosine aminotransferase GREII (TATII) and recombinant GR DBD as well as a fusion protein consisting of the PR DBD fused to Staph. aureus protein-A. GR and PR had identical base contact points, localized within two consecutive major grooves, binding to the same face of the DNA. Ethylation interference was also performed on the GR DBD-TATII interaction. The contact points with the backbone phosphate groups flank the contacts within the major groove for each of the two half-sites. Knowledge of the contact points within the DNA sequence together with the three-dimensional structure of the protein enables modelling of the protein-DNA interaction.

Original languageEnglish (US)
Pages (from-to)598-604
Number of pages7
JournalMolecular Endocrinology
Volume5
Issue number4
DOIs
StatePublished - Apr 1991

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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