General Information

Database accession: MF2201001

Name: Nuclear receptor coactivators CBP and ACTR

PDB ID: 1kbh PDB

Experimental method: NMR

Assembly: heterodimer

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

PMID: 11823864 PubMed

Abstract:

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.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

histone acetyltransferase activity Catalysis of the reaction: acetyl-CoA + histone = CoA + acetyl-histone. GeneOntology

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. GeneOntology

Biological process:

histone acetylation The modification of a histone by the addition of an acetyl group. GeneOntology

transcription, DNA-templated The cellular synthesis of RNA on a template of DNA. GeneOntology

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. GeneOntology

Cellular component:

cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GeneOntology

nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus. GeneOntology

nuclear chromatin The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome in the nucleus. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

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

Chain A

Name: Nuclear receptor coactivator 3

Source organism: Homo sapiens

Length: 47 residues

Sequence:Sequence according to PDB SEQRESEGQSDERALLDQLHTLLSNTDATGLEEIDRALGIPELVNQGQALEPK

UniProtKB AC: Q9Y6Q9 (positions: 1045-1091) UniProt Coverage: 3.3%

UniRef90 AC: UniRef90_Q9Y6Q9 (positions: 1045-1091) UniRef90

Chain B

Name: CREB-binding protein

Source organism: Mus musculus

Length: 59 residues

Sequence:Sequence according to PDB SEQRESPNRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQ

UniProtKB AC: P45481 (positions: 2059-2117) UniProt Coverage: 2.4%

UniRef90 AC: UniRef90_Q92793 (positions: 2058-2116) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Complex evidence:

The interacting monomers have been described to undergo mutual synergistic folding upon binding (PMID: 11823864).

Chain A:

The 1018-1088 region described in DisProt entry DP00343 and the 1018-1088 region described in IDEAL entry IID00110 cover 100% of the sequence present in the structure.

Chain B:

The 2059-2152 region described in DisProt entry DP00348 and the 2057-2117 region described in IDEAL entry IID50008 cover 100% of the sequence present in the structure.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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