Database accession: MF2201002
Name: CBP nuclear coactivator binding domain in complex with p53 TAD
PDB ID: 2l14
Experimental method: NMR
Source organism: Mus musculus / Homo sapiens
Primer publication of the structure:
Lee CW, Martinez-Yamout MA, Dyson HJ, Wright PE
Structure of the p53 transactivation domain in complex with the nuclear receptor coactivator binding domain of CREB binding protein.
(2010) Biochemistry 49: 9964-71
The activity and stability of the tumor suppressor p53 are regulated by interactions with key cellular proteins such as MDM2 and CBP/p300. The transactivation domain (TAD) of p53 contains two subdomains (AD1 and AD2) and interacts directly with the N-terminal domain of MDM2 and with several domains of CBP/p300. Here we report the NMR structure of the full-length p53 TAD in complex with the nuclear coactivator binding domain (NCBD) of CBP. Both the p53 TAD and NCBD are intrinsically disordered and fold synergistically upon binding, as evidenced by the observed increase in helicity and increased level of dispersion of the amide proton resonances. The p53 TAD folds to form a pair of helices (denoted Pα1 and Pα2), which extend from Phe19 to Leu25 and from Pro47 to Trp53, respectively. In the complex, the NCBD forms a bundle of three helices (Cα1, residues 2066-2075; Cα2, residues 2081-2092; and Cα3, residues 2095-2105) with a hydrophobic groove into which p53 helices Pα1 and Pα2 dock. The polypeptide chain between the p53 helices remains flexible and makes no detectable intermolecular contacts with the NCBD. Complex formation is driven largely by hydrophobic contacts that form a stable intermolecular hydrophobic core. A salt bridge between D49 of p53 and R2105 of NCBD may contribute to the binding specificity. The structure provides the first insights into simultaneous binding of the AD1 and AD2 motifs to a target protein.
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Interacting selectively and non-covalently with a sequence of DNA that is in the transcription regulatory region for RNA polymerase II (RNAP II) in order to activate or increase the frequency, rate or extent of transcription from the RNAP II promoter.
RNA polymerase II transcription factor binding Interacting selectively and non-covalently with an RNA polymerase II transcription factor, any protein required to initiate or regulate transcription by RNA polymerase II.
damaged DNA binding Interacting selectively and non-covalently with damaged DNA.
chromatin binding Interacting selectively and non-covalently with chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
zinc ion binding Interacting selectively and non-covalently with zinc (Zn) ions.
negative regulation of transcription from RNA polymerase II promoter Any process that stops, prevents, or reduces the frequency, rate or extent of transcription from an RNA polymerase II promoter.
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.
cellular response to UV Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ultraviolet radiation (UV light) stimulus. Ultraviolet radiation is electromagnetic radiation with a wavelength in the range of 10 to 380 nanometers.
transcription from RNA polymerase II promoter The synthesis of RNA from a DNA template by RNA polymerase II, originating at an RNA polymerase II promoter. Includes transcription of messenger RNA (mRNA) and certain small nuclear RNAs (snRNAs).
PML body A class of nuclear body; they react against SP100 auto-antibodies (PML, promyelocytic leukemia); cells typically contain 10-30 PML bodies per nucleus; alterations in the localization of PML bodies occurs after viral infection.
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: 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)
Name: Cellular tumor antigen p53
Source organism: Homo sapiens
Length: 49 residues
Sequence:Sequence according to PDB SEQRESPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPD
UniProtKB AC: P04637 (positions: 13-61)Coverage: 12.5%
UniRef90 AC: UniRef90_P04637 (positions: 13-61)
No related structure was found in the Protein Data Bank.