1kbh
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Mutual Synergistic Folding in the Interaction Between Nuclear Receptor Coactivators CBP and ACTR
OverviewOverview
Nuclear hormone receptors are ligand-activated transcription factors that, regulate the expression of genes that are essential for development, reproduction and homeostasis. The hormone response is mediated through, recruitment of p160 receptor coactivators and the general transcriptional, coactivator CBP/p300, which function synergistically to activate, transcription. These coactivators exhibit intrinsic histone, acetyltransferase activity, function in the remodelling of chromatin, and, facilitate the recruitment of RNA polymerase II and the basal, transcription machinery. The activities of the p160 coactivators are, dependent on CBP. Both coactivators are essential for proper cell-cycle, control, differentiation and apoptosis, and are implicated in cancer and, other diseases. To elucidate the molecular basis of assembling the, multiprotein activation complex, we undertook a structural and, thermodynamic analysis of the interaction domains of CBP and the activator, for thyroid hormone and retinoid receptors. Here we show that although the, isolated domains are intrinsically disordered, they combine with high, affinity to form a cooperatively folded helical heterodimer. Our study, uncovers a unique mechanism, called 'synergistic folding', through which, p160 coactivators recruit CBP/p300 to allow transmission of the hormonal, signal to the transcriptional machinery.
About this StructureAbout this Structure
1KBH is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators., Demarest SJ, Martinez-Yamout M, Chung J, Chen H, Xu W, Dyson HJ, Evans RM, Wright PE, Nature. 2002 Jan 31;415(6871):549-53. PMID:11823864
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