2J10

p53 tetramerization domain mutant T329F Q331K

2J10 の概要

• エントリーDOI: 10.2210/pdb2j10/pdb
• 関連するPDBエントリー: 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情報: BMRB: 7252
• 分子名称: CELLULAR TUMOR ANTIGEN P53 (1 entity in total)
• 機能のキーワード: 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
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 15253.37

構造登録者

Carbajo, R.J.,Mora, P.,Sanchez del Pino, M.M.,Perez-Paya, E.,Pineda-Lucena, A. (登録日: 2006-08-08, 公開日: 2007-08-28, 最終更新日: 2024-05-15)

主引用文献

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

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: 18076077
DOI: 10.1002/prot.21854

実験手法

SOLUTION NMR