PDBsum entry 2j10

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Transcription PDB id
Protein chains
31 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription
Title: P53 tetramerization domain mutant t329f q331k
Structure: Cellular tumor antigen p53. Chain: a, b, c, d. Fragment: tetramerization domain, residues 326-356. Synonym: tumor suppressor p53, phosphoprotein p53, antigen ny-co-13, p53. Mutation: yes
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Other_details: chemical synthesis
NMR struc: 30 models
Authors: R.J.Carbajo,P.Mora,M.M.Sanchez Del Pino,E.Perez-Paya, A.Pineda-Lucena
Key ref:
P.Mora et al. (2008). 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. PubMed id: 18076077 DOI: 10.1002/prot.21854
08-Aug-06     Release date:   28-Aug-07    
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Protein chains
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
393 a.a.
31 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     apoptotic process   3 terms 
  Biochemical function     DNA binding     2 terms  


DOI no: 10.1002/prot.21854 Proteins 71:1670-1685 (2008)
PubMed id: 18076077  
Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53--a structural and combinatorial approach.
P.Mora, R.J.Carbajo, A.Pineda-Lucena, M.M.Sánchez del Pino, E.Pérez-Payá.
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.
  Selected figure(s)  
Figure 1.
Figure 1. Tetramerization domain of the p53TD. The amino acid sequence of the tetramerization domain of p53 is shown in the top panel where X[n], denotes the combinatorialized positions that replace Tyr^327 (X[1]); Thr^329 (X[2]) and Gln^331 (X[3]) in the original sequence. The arrow and the rectangle cover those amino acids present in the -strand and in the -helix, respectively, of the structure of a monomer of p53TD. The structure of p53TD is shown in the bottom panel. The residues involved in the stabilization of the dimer and tetramer are indicated in grey and yellow, respectively. The mutated solvent-exposed residues of the -sheet are indicated in blue (chains A and C) and green (chains B and D). Databank file code 1sak.
Figure 7.
Figure 7. Detail of the NMR structures of p53TD (A), p53YFK (B), and p53SGG (C), showing the side-chain to side-chain interaction of the residues located in the antiparallel -sheet. The strands of each monomer are colored in green and orange.
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 71, 1670-1685) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21172423 A.S.Bayden, V.A.Yakovlev, P.R.Graves, R.B.Mikkelsen, and G.E.Kellogg (2011).
Factors influencing protein tyrosine nitration--structure-based predictive models.
  Free Radic Biol Med, 50, 749-762.  
  20516128 A.C.Joerger, and A.R.Fersht (2010).
The tumor suppressor p53: from structures to drug discovery.
  Cold Spring Harb Perspect Biol, 2, a000919.  
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