2K8F

Structural Basis for the Regulation of p53 Function by p300

Summary for 2K8F

• Entry DOI: 10.2210/pdb2k8f/pdb
• NMR Information: BMRB: 15944
• Descriptor: Histone acetyltransferase p300, Cellular tumor antigen p53 (2 entities in total)
• Functional Keywords: complex of p53 and p300, acetylation, bromodomain, cell cycle, chromosomal rearrangement, citrullination, disease mutation, host-virus interaction, metal-binding, methylation, nucleus, phosphoprotein, polymorphism, transcription, transcription regulation, transferase, zinc, zinc-finger, activator, alternative splicing, anti-oncogene, apoptosis, covalent protein-rna linkage, cytoplasm, dna-binding, endoplasmic reticulum, glycoprotein, li-fraumeni syndrome, ubl conjugation, transferase-transcription complex, transferase/transcription
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q09472; Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 2
• Total formula weight: 14315.56

Authors

Bai, Y.,Feng, H.,Jenkins, L.M.,Durell, S.R.,Wiodawer, A.,Appella, E. (deposition date: 2008-09-08, release date: 2009-03-03, Last modification date: 2024-05-22)

Primary citation

Feng, H.,Jenkins, L.M.,Durell, S.R.,Hayashi, R.,Mazur, S.J.,Cherry, S.,Tropea, J.E.,Miller, M.,Wlodawer, A.,Appella, E.,Bai, Y.
Structural Basis for p300 Taz2-p53 TAD1 Binding and Modulation by Phosphorylation.
Structure, 17:202-210, 2009

PubMed Abstract: Coactivators CREB-binding protein and p300 play important roles in mediating the transcriptional activity of p53. Until now, however, no detailed structural information has been available on how any of the domains of p300 interact with p53. Here, we report the NMR structure of the complex of the Taz2 (C/H3) domain of p300 and the N-terminal transactivation domain of p53. In the complex, p53 forms a short alpha helix and interacts with the Taz2 domain through an extended surface. Mutational analyses demonstrate the importance of hydrophobic residues for complex stabilization. Additionally, they suggest that the increased affinity of Taz2 for p53(1-39) phosphorylated at Thr(18) is due in part to electrostatic interactions of the phosphate with neighboring arginine residues in Taz2. Thermodynamic experiments revealed the importance of hydrophobic interactions in the complex of Taz2 with p53 phosphorylated at Ser(15) and Thr(18).

PubMed: 19217391
DOI: 10.1016/j.str.2008.12.009

Experimental method

SOLUTION NMR