General Information

Database accession: MF2201002 Original MFIB entry

Name: CBP nuclear coactivator binding domain in complex with p53 TAD

PDB ID: 2l14 PDBe

Experimental method: NMR

Assembly: Heterodimer

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

PMID: 20961098 PubMed

Abstract:

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.


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

Molecular function:

transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding DNA-binding transcription activator activity, RNA polymerase II-specific GeneOntology

RNA polymerase II transcription factor bindingGeneOntology

p53 binding p53 binding GeneOntology

damaged DNA binding damaged DNA binding GeneOntology

chromatin binding chromatin binding GeneOntology

zinc ion binding zinc ion binding GeneOntology

Biological process:

negative regulation of transcription from RNA polymerase II promoter negative regulation of transcription by RNA polymerase II GeneOntology

rhythmic process rhythmic process GeneOntology

positive regulation of transcription from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II GeneOntology

cellular response to UV cellular response to UV GeneOntology

transcription from RNA polymerase II promoter transcription by RNA polymerase II GeneOntology

Cellular component:

cytoplasm cytoplasm GeneOntology

nuclear chromatinGeneOntology

PML body PML body 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: CREB-binding protein

Source organism: Mus musculus

Length: 2441 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMAENLLDGPPNPKRAKLSSPGFSANDNTDFGSLFDLENDLPDELIPNGELSLLNSGNLVPDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSTNMASLGAMGKSPLNQGDSSTPNLPKQAASTSGPTPPASQALNPQAQKQVGLVTSSPATSQTGPGICMNANFNQTHPGLLNSNSGHSLMNQAQQGQAQVMNGSLGAAGRGRGAGMPYPAPAMQGATSSVLAETLTQVSPQMAGHAGLNTAQAGGMTKMGMTGTTSPFGQPFSQTGGQQMGATGVNPQLASKQSMVNSLPAFPTDIKNTSVTTVPNMSQLQTSVGIVPTQAIATGPTADPEKRKLIQQQLVLLLHAHKCQRREQANGEVRACSLPHCRTMKNVLNHMTHCQAGKACQVAHCASSRQIISHWKNCTRHDCPVCLPLKNASDKRNQQTILGSPASGIQNTIGSVGAGQQNATSLSNPNPIDPSSMQRAYAALGLPYMNQPQTQLQPQVPGQQPAQPPAHQQMRTLNALGNNPMSIPAGGITTDQQPPNLISESALPTSLGATNPLMNDGSNSGNIGSLSTIPTAAPPSSTGVRKGWHEHVTQDLRSHLVHKLVQAIFPTPDPAALKDRRMENLVAYAKKVEGDMYESANSRDEYYHLLAEKIYKIQKELEEKRRSRLHKQGILGNQPALPASGAQPPVIPPAQSVRPPNGPLPLPVNRMQVSQGMNSFNPMSLGNVQLPQAPMGPRAASPMNHSVQMNSMASVPGMAISPSRMPQPPNMMGTHANNIMAQAPTQNQFLPQNQFPSSSGAMSVNSVGMGQPAAQAGVSQGQVPGAALPNPLNMLAPQASQLPCPPVTQSPLHPTPPPASTAAGMPSLQHPTAPGMTPPQPAAPTQPSTPVSSGQTPTPTPGSVPSAAQTQSTPTVQAAAQAQVTPQPQTPVQPPSVATPQSSQQQPTPVHTQPPGTPLSQAAASIDNRVPTPSSVTSAETSSQQPGPDVPMLEMKTEVQTDDAEPEPTESKGEPRSEMMEEDLQGSSQVKEETDTTEQKSEPMEVEEKKPEVKVEAKEEEENSSNDTASQSTSPSQPRKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVDPQLLGIPDYFDIVKNPMDLSTIKRKLDTGQYQEPWQYVDDVWLMFNNAWLYNRKTSRVYKFCSKLAEVFEQEIDPVMQSLGYCCGRKYEFSPQTLCCYGKQLCTIPRDAAYYSYQNRYHFCEKCFTEIQGENVTLGDDPSQPQTTISKDQFEKKKNDTLDPEPFVDCKECGRKMHQICVLHYDIIWPSGFVCDNCLKKTGRPRKENKFSAKRLQTTRLGNHLEDRVNKFLRRQNHPEAGEVFVRVVASSDKTVEVKPGMKSRFVDSGEMSESFPYRTKALFAFEEIDGVDVCFFGMHVQNTALIAPHQIQGRVYISYLDSIHFFRPRCLRTAVYHEILIGYLEYVKKLGYVTGHIWACPPSEGDDYIFHCHPPDQKIPKPKRLQEWYKKMLDKAFAERIINDYKDIFKQANEDRLTSAKELPYFEGDFWPNVLEESIKELEQEEEERKKEESTAASETPEGSQGDSKNAKKKNNKKTNKNKSSISRANKKKPSMPNVSNDLSQKLYATMEKHKEVFFVIHLHAGPVISTQPPIVDPDPLLSCDLMDGRDAFLTLARDKHWEFSSLRRSKWSTLCMLVELHTQGQDRFVYTCNECKHHVETRWHCTVCEDYDLCINCYNTKSHTHKMVKWGLGLDDEGSSQGEPQSKSPQESRRLSIQRCIQSLVHACQCRNANCSLPSCQKMKRVVQHTKGCKRKTNGGCPVCKQLIALCCYHAKHCQENKCPVPFCLNIKHKLRQQQIQHRLQQAQLMRRRMATMNTRNVPQQSLPSPTSAPPGTPTQQPSTPQTPQPPAQPQPSPVNMSPAGFPNVARTQPPTIVSAGKPTNQVPAPPPPAQPPPAAVEAARQIEREAQQQQHLYRANINNGMPPGRAGMGTPGSQMTPVGLNVPRPNQVSGPVMSSMPPGQWQQAPIPQQQPMPGMPRPVMSMQAQAAVAGPRMPNVQPPRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQPQPGLQSQPGMQPQPGMHQQPSLQNLNAMQAGVPRPGVPPPQPAMGGLNPQGQALNIMNPGHNPNMTNMNPQYREMVRRQLLQHQQQQQQQQQQQQQQQNSASLAGGMAGHSQFQQPQGPGGYAPAMQQQRMQQHLPIQGSSMGQMAAPMGQLGQMGQPGLGADSTPNIQQALQQRILQQQQMKQQIGSPGQPNPMSPQQHMLSGQPQASHLPGQQIATSLSNQVRSPAPVQSPRPQSQPPHSSPSPRIQPQPSPHHVSPQTGSPHPGLAVTMASSMDQGHLGNPEQSAMLPQLNTPNRSALSSELSLVGDTTGDTLEKFVEGL

UniProtKB AC: P45481 (positions: 2059-2117) UniProt

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

Chain B

Name: Cellular tumor antigen p53

Source organism: Homo sapiens

Length: 393 residues

Sequence:Sequence according to the corresponding UniProt protein segmentMEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD

UniProtKB AC: P04637 (positions: 13-61) UniProt

UniRef90 AC: UniRef90_P04637 (positions: 13-61) UniRef90

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

Evidence level: Direct evidence

Complex Evidence:

None

Chain A:

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.

Chain B:

The 1-73 region described in DisProt entry DP00086 and the 1-96 region described in IDEAL entry IID00015 cover 100% of the sequence present in the structure.

The molecule viewer shows the original PDB stucture.
Only the first NMR model was loaded.

Download the CIF file (.gz.cif)

Download this entry's XML file (.xml)