2j11
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P53 TETRAMERIZATION DOMAIN MUTANT Y327S T329G Q331G
OverviewOverview
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. Proteins 2007. (c) 2007 Wiley-Liss, Inc.
About this StructureAbout this Structure
2J11 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53-A structural and combinatorial approach., Mora P, Carbajo RJ, Pineda-Lucena A, Sanchez Del Pino MM, Perez-Paya E, Proteins. 2007 Dec 12;. PMID:18076077
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- Single protein
- Carbajo, R.J.
- Mora, P.
- Perez-Paya, E.
- Pineda-Lucena, A.
- Pino, M.M.Sanchez.Del.
- Acetylation
- Activator
- Alternative splicing
- Anti-oncogene
- Apoptosis
- Cell cycle
- Disease mutation
- Dna-binding
- Glycoprotein
- Host-virus interaction
- Li-fraumeni syndrome
- Metal-binding
- Mutant
- Nuclear protein
- P53
- Phosphorylation
- Polymorphism
- Tetramerization domain
- Transcription
- Transcription regulation
- Zinc