The Conformation of the Glucocorticoid Receptor AF1/taul Domain Induced by Osmolyte Binds Co-regulatory Proteins

Raj Kumar, J. Ching Lee, D. Wayne Bolen, E. Brad Thompson

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The activation domains of many transcription factors appear to exist naturally in an unfolded or only partially folded state. This seems to be the case for AF1/taul, the major transactivation domain of the human glucocorticoid receptor. We show here that in buffers containing the natural osmolyte trimethylamine N-oxide (TMAO), recombinant AF1 folds into more a compact structure, as evidenced by altered fluorescence emission, circular dichroism spectra, and ultracentrifugal analysis. This conformational transition is cooperative, a characteristic of proteins folding to natural structures. The structure resulting from incubation in TMAO causes the peptide to resist proteolysis by trypsin, chymotrypsin, endoproteinase Arg-C and endoproteinase Gluc-C. Ultracentrifugation studies indicate that AF1/taul exists as a monomer in aqueous solution and that the presence of TMAO does not lead to oligomerization or aggregation. It has been suggested that recombinant AF1 binds both the ubiquitous coactivator CBP and the TATA box-binding protein, TBP. Interactions with both of these are greatly enhanced in the presence of TMAO. Co-immunoadsorption experiments indicate that in TMAO each of these and the coactivator SRC-1 are found complexed with AF1. These data indicate that TMAO induces a conformation in AF1/taul that is important for its interaction with certain co-regulatory proteins.

Original languageEnglish (US)
Pages (from-to)18146-18152
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
StatePublished - Jan 25 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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