Database accession: MF2201001
Name: Nuclear receptor coactivators CBP and ACTR
PDB ID: 1kbh
Experimental method: NMR
Source organism: Homo sapiens / Mus musculus
Primer publication of the structure:
Demarest SJ, Martinez-Yamout M, Chung J, Chen H, Xu W, Dyson HJ, Evans RM, Wright PE
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators.
(2002) Nature 415: 549-53
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.
histone acetyltransferase activity Catalysis of the reaction: acetyl-CoA + histone = CoA + acetyl-histone.
transcription coactivator activity Interacting selectively and non-covalently with a activating transcription factor and also with the basal transcription machinery in order to increase the frequency, rate or extent of transcription. Cofactors generally do not bind the template nucleic acid, but rather mediate protein-protein interactions between activating transcription factors and the basal transcription machinery.
histone acetylation The modification of a histone by the addition of an acetyl group.
transcription, DNA-templated The cellular synthesis of RNA on a template of DNA.
positive regulation of transcription from RNA polymerase II promoter Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
Number of unique protein segments: 2
Name: Nuclear receptor coactivator 3
Source organism: Homo sapiens
Length: 47 residues
Sequence:Sequence according to PDB SEQRESEGQSDERALLDQLHTLLSNTDATGLEEIDRALGIPELVNQGQALEPK
UniProtKB AC: Q9Y6Q9 (positions: 1045-1091)Coverage: 3.3%
UniRef90 AC: UniRef90_Q9Y6Q9 (positions: 1045-1091)
Name: CREB-binding protein
Source organism: Mus musculus
Length: 59 residues
Sequence:Sequence according to PDB SEQRESPNRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQ
UniProtKB AC: P45481 (positions: 2059-2117)Coverage: 2.4%
UniRef90 AC: UniRef90_Q92793 (positions: 2058-2116)
The interacting monomers have been described to undergo mutual synergistic folding upon binding (PMID: 11823864).
No related structure was found in the Protein Data Bank.