Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumour suppressor p53 tetramerization domain.


Abstract

The contribution of almost each amino acid side chain to the thermodynamic stability of the tetramerization domain (residues 326-353) of human p53 has been quantitated using 25 mutants with single-residue truncations to alanine (or glycine). Truncation of either Leu344 or Leu348 buried at the tetramer interface, but not of any other residue, led to the formation of dimers of moderate stability (8-9 kcal/mol of dimer) instead of tetramers. One-third of the substitutions were moderately destabilizing (<3.9 kcal/mol of tetramer). Truncations of Arg333, Asn345 or Glu349 involved in intermonomer hydrogen bonds, Ala347 at the tetramer interface or Thr329 were more destabilizing (4.1-5.7 kcal/mol). Strongly destabilizing (8.8- 11.7 kcal/mol) substitutions included those of Met340 at the tetramer interface and Phe328, Arg337 and Phe338 involved peripherally in the hydrophobic core. Truncation of any of the three residues involved centrally in the hydrophobic core of each primary dimer either prevented folding (Ile332) or allowed folding only at high protein concentration or low temperature (Leu330 and Phe341). Nine hydrophobic residues per monomer constitute critical determinants for the stability and oligomerization status of this p53 domain.

Submission Details

ID: vEnB52Cr3

Submitter: Shu-Ching Ou

Submission Date: Aug. 7, 2018, 12:26 p.m.

Version: 1

Publication Details
Mateu MG;Fersht AR,EMBO J (1998) Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumour suppressor p53 tetramerization domain. PMID:9582268
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1A1U 1997-12-16T00:00:00+0000 0 SOLUTION STRUCTURE DETERMINATION OF A P53 MUTANT DIMERIZATION DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE
1AIE 1997-04-17T00:00:00+0000 1.5 P53 TETRAMERIZATION DOMAIN CRYSTAL STRUCTURE
1C26 1999-07-22T00:00:00+0000 1.7 CRYSTAL STRUCTURE OF P53 TETRAMERIZATION DOMAIN
1DT7 2000-01-11T00:00:00+0000 0 SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)
1GZH 2002-05-22T00:00:00+0000 2.6 Crystal structure of the BRCT domains of human 53BP1 bound to the p53 tumor supressor
1GZH 2002-05-22T00:00:00+0000 2.6 Crystal structure of the BRCT domains of human 53BP1 bound to the p53 tumor supressor
1H26 2002-07-31T00:00:00+0000 2.24 CDK2/CyclinA in complex with an 11-residue recruitment peptide from p53
1HS5 2000-12-22T00:00:00+0000 0 NMR SOLUTION STRUCTURE OF DESIGNED P53 DIMER
1JSP 2001-08-17T00:00:00+0000 0 NMR Structure of CBP Bromodomain in complex with p53 peptide
1KZY 2002-02-08T00:00:00+0000 2.5 Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Cellular tumor antigen p53 P04637 P53_HUMAN
95.2 Cellular tumor antigen p53 P13481 P53_CHLAE
95.7 Cellular tumor antigen p53 P56423 P53_MACFA
95.7 Cellular tumor antigen p53 P61260 P53_MACFU
95.7 Cellular tumor antigen p53 P56424 P53_MACMU
93.1 Cellular tumor antigen p53 Q9TTA1 P53_TUPBE