2J10
p53 tetramerization domain mutant T329F Q331K
Summary for 2J10
Entry DOI | 10.2210/pdb2j10/pdb |
Related | 1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAG 1SAH 1SAI 1SAJ 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YCQ 1YCR 1YCS 2AC0 2ADY 2AHI 2ATA 2B3G 2BIM 2BIN 2BIO 2BIP 2BIQ 2F1X 2FEJ 2J0Z 2J11 3SAK |
NMR Information | BMRB: 7252 |
Descriptor | CELLULAR TUMOR ANTIGEN P53 (1 entity in total) |
Functional Keywords | p53, zinc, activator, apoptosis, wild type, cell cycle, acetylation, dna-binding, polymorphism, tetramerization domain, transcription regulation, anti-oncogene, nuclear protein, phosphorylation, li-fraumeni syndrome, host-virus interaction, disease mutation, alternative splicing, glycoprotein, transcription, metal-binding |
Biological source | HOMO SAPIENS (HUMAN) |
Cellular location | 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 | 4 |
Total formula weight | 15253.37 |
Authors | Carbajo, R.J.,Mora, P.,Sanchez del Pino, M.M.,Perez-Paya, E.,Pineda-Lucena, A. (deposition date: 2006-08-08, release date: 2007-08-28, Last modification date: 2024-05-15) |
Primary citation | Mora, P.,Carbajo, R.J.,Pineda-Lucena, A.,Sanchez del Pino, M.M.,Perez-Paya, E. Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53--a structural and combinatorial approach. Proteins, 71:1670-1685, 2008 Cited by PubMed Abstract: The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the beta-sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent-exposed residues in the stability of p53TD. PubMed: 18076077DOI: 10.1002/prot.21854 PDB entries with the same primary citation |
Experimental method | SOLUTION NMR |
Structure validation
Download full validation report