PDBsum entry 1sal

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protein Protein-protein interface(s) links
Anti-oncogene PDB id
Protein chains
42 a.a. *
Waters ×12
* Residue conservation analysis
PDB id:
Name: Anti-oncogene
Title: High resolution solution nmr structure of the oligomerization domain of p53 by multi-dimensional nmr (sad structures)
Structure: Tumor suppressor p53. Chain: a, b, c, d. Other_details: minimized average sad structure
Source: Homo sapiens. Human. Organism_taxid: 9606
NMR struc: 1 models
Authors: G.M.Clore,J.G.Omichinski,A.M.Gronenborn
Key ref: G.M.Clore et al. (1995). Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol, 2, 321-333. PubMed id: 7796267
12-Mar-95     Release date:   15-Oct-95    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
393 a.a.
42 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


Nat Struct Biol 2:321-333 (1995)
PubMed id: 7796267  
Refined solution structure of the oligomerization domain of the tumour suppressor p53.
G.M.Clore, J.Ernst, R.Clubb, J.G.Omichinski, W.M.Kennedy, K.Sakaguchi, E.Appella, A.M.Gronenborn.
The NMR solution structure of the oligomerization domain of the tumour suppressor p53 (residues 319-360) has been refined. The structure comprises a dimer of dimers, oriented in an approximately orthogonal manner. The present structure determination is based on 4,472 experimental NMR restraints which represents a three and half fold increase over our previous work in the number of NOE restraints at the tetramerization interface. A comparison with the recently solved 1.7 A resolution X-ray structure shows that the structures are very similar and that the average angular root-mean-square difference in the interhelical angles is about 1 degree. The results of recent extensive mutagenesis data and the possible effects of mutations which have been identified in human cancers are discussed in the light of the present structure.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21522129 T.J.Petty, S.Emamzadah, L.Costantino, I.Petkova, E.S.Stavridi, J.G.Saven, E.Vauthey, and T.D.Halazonetis (2011).
An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity.
  EMBO J, 30, 2167-2176.
PDB codes: 3q01 3q05 3q06
  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.  
20128691 J.Malcikova, B.Tichy, J.Damborsky, J.Kabathova, M.Trbusek, J.Mayer, and S.Pospisilova (2010).
Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation.
  Biol Chem, 391, 197-205.  
21086029 P.W.Chun, and M.S.Lewis (2010).
Planck-Benzinger thermal work function: thermodynamic characterization of the carboxy-terminus of p53 peptide fragments.
  Protein J, 29, 617-630.  
19815500 A.C.Joerger, S.Rajagopalan, E.Natan, D.B.Veprintsev, C.V.Robinson, and A.R.Fersht (2009).
Structural evolution of p53, p63, and p73: implication for heterotetramer formation.
  Proc Natl Acad Sci U S A, 106, 17705-17710.
PDB codes: 2wqi 2wqj 2wtt
19286366 A.L.Okorokov, and E.V.Orlova (2009).
Structural biology of the p53 tumour suppressor.
  Curr Opin Struct Biol, 19, 197-202.  
19933326 F.Huang, S.Rajagopalan, G.Settanni, R.J.Marsh, D.A.Armoogum, N.Nicolaou, A.J.Bain, E.Lerner, E.Haas, L.Ying, and A.R.Fersht (2009).
Multiple conformations of full-length p53 detected with single-molecule fluorescence resonance energy transfer.
  Proc Natl Acad Sci U S A, 106, 20758-20763.  
19121375 L.A.Holbrook, R.A.Butler, R.E.Cashon, and R.J.Van Beneden (2009).
Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.
  Gene, 433, 81-87.  
20030809 T.Brandt, M.Petrovich, A.C.Joerger, and D.B.Veprintsev (2009).
Conservation of DNA-binding specificity and oligomerisation properties within the p53 family.
  BMC Genomics, 10, 628.  
18781628 T.Nomura, R.Kamada, I.Ito, Y.Chuman, Y.Shimohigashi, and K.Sakaguchi (2009).
Oxidation of methionine residue at hydrophobic core destabilizes p53 tetrameric structure.
  Biopolymers, 91, 78-84.  
  19434769 Y.Zhao, X.Q.Chen, and J.Z.Du (2009).
Cellular adaptation to hypoxia and p53 transcription regulation.
  J Zhejiang Univ Sci B, 10, 404-410.  
18410249 A.C.Joerger, and A.R.Fersht (2008).
Structural biology of the tumor suppressor p53.
  Annu Rev Biochem, 77, 557-582.  
18453682 C.Tu, Y.H.Tan, G.Shaw, Z.Zhou, Y.Bai, R.Luo, and X.Ji (2008).
Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 angstroms resolution.
  Acta Crystallogr D Biol Crystallogr, 64, 471-477.
PDB code: 2pcx
18621913 M.M.García-Alai, H.Tidow, E.Natan, F.M.Townsley, D.B.Veprintsev, and A.R.Fersht (2008).
The novel p53 isoform "delta p53" is a misfolded protein and does not bind the p21 promoter site.
  Protein Sci, 17, 1671-1678.  
18391200 M.Wells, H.Tidow, T.J.Rutherford, P.Markwick, M.R.Jensen, E.Mylonas, D.I.Svergun, M.Blackledge, and A.R.Fersht (2008).
Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain.
  Proc Natl Acad Sci U S A, 105, 5762-5767.  
18076077 P.Mora, R.J.Carbajo, A.Pineda-Lucena, M.M.Sánchez del Pino, and E.Pérez-Payá (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.
PDB codes: 2j0z 2j10 2j11
17401432 A.C.Joerger, and A.R.Fersht (2007).
Structure-function-rescue: the diverse nature of common p53 cancer mutants.
  Oncogene, 26, 2226-2242.  
17391014 H.Xie, S.Vucetic, L.M.Iakoucheva, C.J.Oldfield, A.K.Dunker, V.N.Uversky, and Z.Obradovic (2007).
Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.
  J Proteome Res, 6, 1882-1898.  
17804642 K.J.Riley, and L.J.Maher (2007).
p53 RNA interactions: new clues in an old mystery.
  RNA, 13, 1825-1833.  
18087040 R.S.Foo, Y.J.Nam, M.J.Ostreicher, M.D.Metzl, R.S.Whelan, C.F.Peng, A.W.Ashton, W.Fu, K.Mani, S.F.Chin, E.Provenzano, I.Ellis, N.Figg, S.Pinder, M.R.Bennett, C.Caldas, and R.N.Kitsis (2007).
Regulation of p53 tetramerization and nuclear export by ARC.
  Proc Natl Acad Sci U S A, 104, 20826-20831.  
17640907 Z.Shakked (2007).
Quaternary structure of p53: the light at the end of the tunnel.
  Proc Natl Acad Sci U S A, 104, 12231-12232.  
17015838 A.C.Joerger, H.C.Ang, and A.R.Fersht (2006).
Structural basis for understanding oncogenic p53 mutations and designing rescue drugs.
  Proc Natl Acad Sci U S A, 103, 15056-15061.
PDB codes: 2j1w 2j1x 2j1y 2j1z 2j20 2j21
17053786 A.L.Okorokov, M.B.Sherman, C.Plisson, V.Grinkevich, K.Sigmundsson, G.Selivanova, J.Milner, and E.V.Orlova (2006).
The structure of p53 tumour suppressor protein reveals the basis for its functional plasticity.
  EMBO J, 25, 5191-5200.  
16461914 D.B.Veprintsev, S.M.Freund, A.Andreeva, S.E.Rutledge, H.Tidow, J.M.Cañadillas, C.M.Blair, and A.R.Fersht (2006).
Core domain interactions in full-length p53 in solution.
  Proc Natl Acad Sci U S A, 103, 2115-2119.  
16601753 F.Murray-Zmijewski, D.P.Lane, and J.C.Bourdon (2006).
p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress.
  Cell Death Differ, 13, 962-972.  
16575406 G.M.Wahl (2006).
Mouse bites dogma: how mouse models are changing our views of how P53 is regulated in vivo.
  Cell Death Differ, 13, 973-983.  
16757565 H.You, K.Yamamoto, and T.W.Mak (2006).
Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a.
  Proc Natl Acad Sci U S A, 103, 9051-9056.  
20141510 J.Deng, R.Dayam, and N.Neamati (2006).
Patented small molecule inhibitors of p53-MDM2 interaction.
  Expert Opin Ther Pat, 16, 165-188.  
16581806 K.J.Riley, L.A.Cassiday, A.Kumar, and L.J.Maher (2006).
Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid system.
  RNA, 12, 620-630.  
16983711 L.Römer, C.Klein, A.Dehner, H.Kessler, and J.Buchner (2006).
p53--a natural cancer killer: structural insights and therapeutic concepts.
  Angew Chem Int Ed Engl, 45, 6440-6460.  
16793544 M.Kitayner, H.Rozenberg, N.Kessler, D.Rabinovich, L.Shaulov, T.E.Haran, and Z.Shakked (2006).
Structural basis of DNA recognition by p53 tetramers.
  Mol Cell, 22, 741-753.
PDB codes: 2ac0 2ady 2ahi 2ata
16717092 W.C.Ho, M.X.Fitzgerald, and R.Marmorstein (2006).
Structure of the p53 core domain dimer bound to DNA.
  J Biol Chem, 281, 20494-20502.
PDB code: 2geq
16964247 W.H.Yang, J.E.Kim, H.W.Nam, J.W.Ju, H.S.Kim, Y.S.Kim, and J.W.Cho (2006).
Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability.
  Nat Cell Biol, 8, 1074-1083.  
16460008 Y.Higashimoto, Y.Asanomi, S.Takakusagi, M.S.Lewis, K.Uosaki, S.R.Durell, C.W.Anderson, E.Appella, and K.Sakaguchi (2006).
Unfolding, aggregation, and amyloid formation by the tetramerization domain from mutant p53 associated with lung cancer.
  Biochemistry, 45, 1608-1619.  
16291740 Y.Kawaguchi, A.Ito, E.Appella, and T.P.Yao (2006).
Charge modification at multiple C-terminal lysine residues regulates p53 oligomerization and its nucleus-cytoplasm trafficking.
  J Biol Chem, 281, 1394-1400.  
16035029 A.Dehner, C.Klein, S.Hansen, L.Müller, J.Buchner, M.Schwaiger, and H.Kessler (2005).
Cooperative binding of p53 to DNA: regulation by protein-protein interactions through a double salt bridge.
  Angew Chem Int Ed Engl, 44, 5247-5251.  
16138303 A.Dehner, and H.Kessler (2005).
Diffusion NMR spectroscopy: folding and aggregation of domains in p53.
  Chembiochem, 6, 1550-1565.  
15837201 A.Friedler, D.B.Veprintsev, S.M.Freund, K.I.von Glos, and A.R.Fersht (2005).
Modulation of binding of DNA to the C-terminal domain of p53 by acetylation.
  Structure, 13, 629-636.  
15611070 A.Friedler, D.B.Veprintsev, T.Rutherford, K.I.von Glos, and A.R.Fersht (2005).
Binding of Rad51 and other peptide sequences to a promiscuous, highly electrostatic binding site in p53.
  J Biol Chem, 280, 8051-8059.  
15738397 B.Ma, Y.Pan, K.Gunasekaran, R.B.Venkataraghavan, A.J.Levine, and R.Nussinov (2005).
Comparison of the protein-protein interfaces in the p53-DNA crystal structures: towards elucidation of the biological interface.
  Proc Natl Acad Sci U S A, 102, 3988-3993.  
16260757 C.Galea, P.Bowman, and R.W.Kriwacki (2005).
Disruption of an intermonomer salt bridge in the p53 tetramerization domain results in an increased propensity to form amyloid fibrils.
  Protein Sci, 14, 2993-3003.  
16267689 I.Belda, S.Madurga, X.Llorà, M.Martinell, T.Tarragó, M.G.Piqueras, E.Nicolás, and E.Giralt (2005).
ENPDA: an evolutionary structure-based de novo peptide design algorithm.
  J Comput Aided Mol Des, 19, 585-601.  
15723359 J.Duan, and L.Nilsson (2005).
Thermal unfolding simulations of a multimeric protein--transition state and unfolding pathways.
  Proteins, 59, 170-182.  
15921859 L.Latonen, and M.Laiho (2005).
Cellular UV damage responses--functions of tumor suppressor p53.
  Biochim Biophys Acta, 1755, 71-89.  
15613472 P.Müller, P.Ceskova, and B.Vojtesek (2005).
Hsp90 is essential for restoring cellular functions of temperature-sensitive p53 mutant protein but not for stabilization and activation of wild-type p53: implications for cancer therapy.
  J Biol Chem, 280, 6682-6691.  
15863617 W.Feng, J.F.Long, and M.Zhang (2005).
A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
  Proc Natl Acad Sci U S A, 102, 6861-6866.
PDB codes: 1y74 1y76
15358771 L.Müller, A.Schaupp, D.Walerych, H.Wegele, and J.Buchner (2004).
Hsp90 regulates the activity of wild type p53 under physiological and elevated temperatures.
  J Biol Chem, 279, 48846-48854.  
15108353 Y.Sun, X.R.Zeng, L.Wenger, G.S.Firestein, and H.S.Cheung (2004).
P53 down-regulates matrix metalloproteinase-1 by targeting the communications between AP-1 and the basal transcription complex.
  J Cell Biochem, 92, 258-269.  
12433927 R.D.Brokx, E.Bolewska-Pedyczak, and J.Gariépy (2003).
A stable human p53 heterotetramer based on constructive charge interactions within the tetramerization domain.
  J Biol Chem, 278, 2327-2332.  
12826609 S.Kato, S.Y.Han, W.Liu, K.Otsuka, H.Shibata, R.Kanamaru, and C.Ishioka (2003).
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.
  Proc Natl Acad Sci U S A, 100, 8424-8429.  
14639659 X.Agirre, F.J.Novo, M.J.Calasanz, M.J.Larráyoz, I.Lahortiga, M.Valgañón, M.García-Delgado, and J.L.Vizmanos (2003).
TP53 is frequently altered by methylation, mutation, and/or deletion in acute lymphoblastic leukaemia.
  Mol Carcinog, 38, 201-208.  
11793474 A.C.Martin, A.M.Facchiano, A.L.Cuff, T.Hernandez-Boussard, M.Olivier, P.Hainaut, and J.M.Thornton (2002).
Integrating mutation data and structural analysis of the TP53 tumor-suppressor protein.
  Hum Mutat, 19, 149-164.  
11805092 C.D.Nicholls, K.G.McLure, M.A.Shields, and P.W.Lee (2002).
Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect.
  J Biol Chem, 277, 12937-12945.  
11753428 E.L.DiGiammarino, A.S.Lee, C.Cadwell, W.Zhang, B.Bothner, R.C.Ribeiro, G.Zambetti, and R.W.Kriwacki (2002).
A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer.
  Nat Struct Biol, 9, 12-16.  
11222313 A.R.Völkel, and J.Noolandi (2001).
Meanfield approach to the thermodynamics of protein-solvent systems with application to p53.
  Biophys J, 80, 1524-1537.  
11559355 J.L.Neira, and M.G.Mateu (2001).
Hydrogen exchange of the tetramerization domain of the human tumour suppressor p53 probed by denaturants and temperature.
  Eur J Biochem, 268, 4868-4877.  
11481490 R.C.Ribeiro, F.Sandrini, B.Figueiredo, G.P.Zambetti, E.Michalkiewicz, A.R.Lafferty, L.DeLacerda, M.Rabin, C.Cadwell, G.Sampaio, I.Cat, C.A.Stratakis, and R.Sandrini (2001).
An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
  Proc Natl Acad Sci U S A, 98, 9330-9335.  
  10523638 A.L.Okorokov, and J.Milner (1999).
An ATP/ADP-dependent molecular switch regulates the stability of p53-DNA complexes.
  Mol Cell Biol, 19, 7501-7510.  
  10493578 E.S.Stavridi, N.H.Chehab, L.C.Caruso, and T.D.Halazonetis (1999).
Change in oligomerization specificity of the p53 tetramerization domain by hydrophobic amino acid substitutions.
  Protein Sci, 8, 1773-1779.  
10075936 J.M.Stommel, N.D.Marchenko, G.S.Jimenez, U.M.Moll, T.J.Hope, and G.M.Wahl (1999).
A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking.
  EMBO J, 18, 1660-1672.  
10097082 M.G.Mateu, and A.R.Fersht (1999).
Mutually compensatory mutations during evolution of the tetramerization domain of tumor suppressor p53 lead to impaired hetero-oligomerization.
  Proc Natl Acad Sci U S A, 96, 3595-3599.  
10202145 S.Y.Shieh, Y.Taya, and C.Prives (1999).
DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization.
  EMBO J, 18, 1815-1823.  
9600889 G.M.Clore, and A.M.Gronenborn (1998).
New methods of structure refinement for macromolecular structure determination by NMR.
  Proc Natl Acad Sci U S A, 95, 5891-5898.  
9628871 K.G.McLure, and P.W.Lee (1998).
How p53 binds DNA as a tetramer.
  EMBO J, 17, 3342-3350.  
9739174 L.Otvos, R.Hoffmann, Z.Q.Xiang, I.O, H.Deng, M.Wysocka, A.M.Pease, M.E.Rogers, M.Blaszczyk-Thurin, and H.C.Ertl (1998).
A monoclonal antibody to a multiphosphorylated, conformational epitope at the carboxy-terminus of p53.
  Biochim Biophys Acta, 1404, 457-474.  
9582268 M.G.Mateu, and A.R.Fersht (1998).
Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumour suppressor p53 tetramerization domain.
  EMBO J, 17, 2748-2758.  
9254608 K.Sakaguchi, H.Sakamoto, M.S.Lewis, C.W.Anderson, J.W.Erickson, E.Appella, and D.Xie (1997).
Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53.
  Biochemistry, 36, 10117-10124.  
9390024 L.S.Cox (1997).
Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1.
  J Pathol, 183, 134-140.  
9321402 M.McCoy, E.S.Stavridi, J.L.Waterman, A.M.Wieczorek, S.J.Opella, and T.D.Halazonetis (1997).
Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain.
  EMBO J, 16, 6230-6236.
PDB code: 1a1u
9493957 N.Bissonnette, B.Wasylyk, and D.J.Hunting (1997).
The apoptotic and transcriptional transactivation activities of p53 can be dissociated.
  Biochem Cell Biol, 75, 351-358.  
8768898 A.J.Wand, and S.W.Englander (1996).
Protein complexes studied by NMR spectroscopy.
  Curr Opin Biotechnol, 7, 403-408.  
  8762138 J.Kuszewski, A.M.Gronenborn, and G.M.Clore (1996).
Improving the quality of NMR and crystallographic protein structures by means of a conformational database potential derived from structure databases.
  Protein Sci, 5, 1067-1080.  
  8612585 T.Léveillard, L.Andera, N.Bissonnette, L.Schaeffer, L.Bracco, J.M.Egly, and B.Wasylyk (1996).
Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations.
  EMBO J, 15, 1615-1624.  
  8575189 A.M.Gronenborn, and G.M.Clore (1995).
Structures of protein complexes by multidimensional heteronuclear magnetic resonance spectroscopy.
  Crit Rev Biochem Mol Biol, 30, 351-385.  
  7663341 R.T.Clubb, J.G.Omichinski, K.Sakaguchi, E.Appella, A.M.Gronenborn, and G.M.Clore (1995).
Backbone dynamics of the oligomerization domain of p53 determined from 15N NMR relaxation measurements.
  Protein Sci, 4, 855-862.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.