Regulation of the amino-terminal transcription activation domain of progesterone receptor by a cofactor-induced protein folding mechanism.
We previously identified a small basic leucine zipper (bZIP) protein, Jun dimerization protein 2 (JDP-2), that acts as a coregulator of the N-terminal transcriptional activation domain of progesterone receptor (PR). We show here that JDP-2, through interaction with the DNA binding domain (DBD), induces or stabilizes structure in the N-terminal domain in a manner that correlates with JDP-2 stimulation of transcriptional activity. Circular dichroism spectroscopy experiments showed that JDP-2 interaction caused a significant increase in overall helical content of a two-domain PR polypeptide containing the N-terminal domain and DBD and that the change in structure resides primarily in the N-terminal domain. Thermal melt curves showed that the JDP-2/PR complex is significantly more stable than either protein alone, and partial proteolysis confirmed that JDP-2 interaction alters conformation of the N-terminal domain of PR. Functional analysis of N-terminal domain mutants and receptor chimeras provides evidence that the stimulatory effect of JDP-2 on transcriptional activity of PR is mediated through an interdomain communication between the DBD and the N-terminal domain and that transcriptional activity and functional response to JDP-2 are mediated by multiple elements of the N-terminal domain as opposed to a discrete region.
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- Transcriptional Activation
- Repressor Proteins
- Recombinant Fusion Proteins
- Receptors, Progesterone
- Rats
- Protein Structure, Tertiary
- Protein Folding
- Protein Conformation
- Protein Binding
- Peptide Mapping
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcriptional Activation
- Repressor Proteins
- Recombinant Fusion Proteins
- Receptors, Progesterone
- Rats
- Protein Structure, Tertiary
- Protein Folding
- Protein Conformation
- Protein Binding
- Peptide Mapping