PDBsum entry 3kz8

Go to PDB code: 
protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
Protein chains
195 a.a. *
IOD ×2
_ZN ×2
Waters ×312
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Diversity in DNA recognition by p53 revealed by crystal stru with hoogsteen base pairs (p53-DNA complex 3)
Structure: Cellular tumor antigen p53. Chain: a, b. Fragment: p53 core domain, unp residues 94-293. Synonym: tumor suppressor p53, phosphoprotein p53, antigen engineered: yes. DNA (5'- d( Tp Gp Gp Gp Cp Ap Tp Gp Cp Cp Cp Gp Gp Gp Cp Ap Tp Gp Cp 3'). Chain: c.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: tp53. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Other_details: synthetic DNA fragment.
1.91Å     R-factor:   0.223     R-free:   0.266
Authors: H.Rozenberg,O.Suad,Z.Shakked
Key ref: M.Kitayner et al. (2010). Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol, 17, 423-429. PubMed id: 20364130
08-Dec-09     Release date:   31-Mar-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
393 a.a.
195 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   2 terms 
  Biochemical function     transcription regulatory region DNA binding     3 terms  


Nat Struct Mol Biol 17:423-429 (2010)
PubMed id: 20364130  
Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs.
M.Kitayner, H.Rozenberg, R.Rohs, O.Suad, D.Rabinovich, B.Honig, Z.Shakked.
p53 binds as a tetramer to DNA targets consisting of two decameric half-sites separated by a variable spacer. Here we present high-resolution crystal structures of complexes between p53 core-domain tetramers and DNA targets consisting of contiguous half-sites. In contrast to previously reported p53-DNA complexes that show standard Watson-Crick base pairs, the newly reported structures show noncanonical Hoogsteen base-pairing geometry at the central A-T doublet of each half-site. Structural and computational analyses show that the Hoogsteen geometry distinctly modulates the B-DNA helix in terms of local shape and electrostatic potential, which, together with the contiguous DNA configuration, results in enhanced protein-DNA and protein-protein interactions compared to noncontiguous half-sites. Our results suggest a mechanism relating spacer length to protein-DNA binding affinity. Our findings also expand the current understanding of protein-DNA recognition and establish the structural and chemical properties of Hoogsteen base pairs as the basis for a novel mode of sequence readout.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21350476 B.Honig, and R.Rohs (2011).
Biophysics: Flipping Watson and Crick.
  Nature, 470, 472-473.  
21464285 C.Chen, N.Gorlatova, Z.Kelman, and O.Herzberg (2011).
Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements.
  Proc Natl Acad Sci U S A, 108, 6456-6461.
PDB codes: 3qym 3qyn
21270796 E.N.Nikolova, E.Kim, A.A.Wise, P.J.O'Brien, I.Andricioaei, and H.M.Al-Hashimi (2011).
Transient Hoogsteen base pairs in canonical duplex DNA.
  Nature, 470, 498-502.  
21071400 I.Beno, K.Rosenthal, M.Levitine, L.Shaulov, and T.E.Haran (2011).
Sequence-dependent cooperative binding of p53 to DNA targets and its relationship to the structural properties of the DNA targets.
  Nucleic Acids Res, 39, 1919-1932.  
21240404 K.M.Schlitt, A.L.Millen, S.D.Wetmore, and R.A.Manderville (2011).
An indole-linked C8-deoxyguanosine nucleoside acts as a fluorescent reporter of Watson-Crick versus Hoogsteen base pairing.
  Org Biomol Chem, 9, 1565-1571.  
21338609 N.Khazanov, and Y.Levy (2011).
Sliding of p53 along DNA can be modulated by its oligomeric state and by cross-talks between its constituent domains.
  J Mol Biol, 408, 335-355.  
21178074 R.Melero, S.Rajagopalan, M.Lázaro, A.C.Joerger, T.Brandt, D.B.Veprintsev, G.Lasso, D.Gil, S.H.Scheres, J.M.Carazo, A.R.Fersht, and M.Valle (2011).
Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNA.
  Proc Natl Acad Sci U S A, 108, 557-562.  
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
20696896 D.Coutandin, H.D.Ou, F.Löhr, and V.Dötsch (2010).
Tracing the protectors path from the germ line to the genome.
  Proc Natl Acad Sci U S A, 107, 15318-15325.  
20878668 J.L.Kaar, N.Basse, A.C.Joerger, E.Stephens, T.J.Rutherford, and A.R.Fersht (2010).
Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding.
  Protein Sci, 19, 2267-2278.  
  20514355 L.Jiang, M.S.Sheikh, and Y.Huang (2010).
Decision Making by p53: Life versus Death.
  Mol Cell Pharmacol, 2, 69-77.  
20334529 R.Rohs, X.Jin, S.M.West, R.Joshi, B.Honig, and R.S.Mann (2010).
Origins of specificity in protein-DNA recognition.
  Annu Rev Biochem, 79, 233-269.  
21106075 R.Torella, E.Moroni, M.Caselle, G.Morra, and G.Colombo (2010).
Investigating dynamic and energetic determinants of protein nucleic acid recognition: analysis of the zinc finger zif268-DNA complexes.
  BMC Struct Biol, 10, 42.  
20368720 S.Chitayat, and C.H.Arrowsmith (2010).
Four p(53)s in a pod.
  Nat Struct Mol Biol, 17, 390-391.  
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.