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PDBsum entry 1f9f
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protein ligands Protein-protein interface(s) links
Transcription PDB id
1f9f

 

 

 

 

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Contents
Protein chains
76 a.a. *
77 a.a. *
76 a.a. *
82 a.a. *
Ligands
SO4 ×2
Waters ×99
* Residue conservation analysis
PDB id:
1f9f
Name: Transcription
Title: Crystal structure of the hpv-18 e2 DNA-binding domain
Structure: Regulatory protein e2. Chain: a, b, c, d. Fragment: residues 287-365 of hpv-18 e2 with gshm. Engineered: yes
Source: Human papillomavirus type 18. Organism_taxid: 333761. Gene: e2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Not given
Resolution:
1.90Å     R-factor:   0.237     R-free:   0.294
Authors: S.S.Kim,J.Tam,A.F.Wang,R.Hegde
Key ref:
S.S.Kim et al. (2000). The structural basis of DNA target discrimination by papillomavirus E2 proteins. J Biol Chem, 275, 31245-31254. PubMed id: 10906136 DOI: 10.1074/jbc.M004541200
Date:
10-Jul-00     Release date:   15-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06790  (VE2_HPV18) -  Regulatory protein E2 from Human papillomavirus type 18
Seq:
Struc: 		365 a.a.
76 a.a.*
Protein chain
Pfam   ArchSchema ?
P06790  (VE2_HPV18) -  Regulatory protein E2 from Human papillomavirus type 18
Seq:
Struc: 		365 a.a.
77 a.a.*
Protein chain
Pfam   ArchSchema ?
P06790  (VE2_HPV18) -  Regulatory protein E2 from Human papillomavirus type 18
Seq:
Struc: 		365 a.a.
76 a.a.*
Protein chain
Pfam   ArchSchema ?
P06790  (VE2_HPV18) -  Regulatory protein E2 from Human papillomavirus type 18
Seq:
Struc: 		365 a.a.
82 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 11 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1074/jbc.M004541200 J Biol Chem 275:31245-31254 (2000)
PubMed id: 10906136  
 
 
The structural basis of DNA target discrimination by papillomavirus E2 proteins.
S.S.Kim, J.K.Tam, A.F.Wang, R.S.Hegde.
 
  ABSTRACT  
 
The papillomavirus E2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral DNA replication. Disruption of the E2 gene is commonly associated with malignancy in cervical carcinoma, indicating that E2 has a role in regulating tumor progression. Although the E2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair DNA sequence, the cancer-associated human papillomavirus E2 proteins display a unique ability to detect DNA flexibility and intrinsic curvature. To understand the structural basis for this phenomenon, we have determined the crystal structures of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the E2-DNA interaction is accompanied by a large deformation of the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in both high and low affinity complexes. The differences in affinity correlate with the flexibility of the DNA sequence. Preferences of E2 proteins from different papillomavirus strains for flexible or prevent DNA targets correlate with the distribution of positive charge on their DNA interaction surfaces, suggesting a role for electrostatic forces in the recognition of DNA deformability.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Design of oligonucleotides used. 		Figure 6.
Fig. 6. a, comparison of the HPV-18 E2/D protein in the free (green) and DNA-bound (gold) states. The left subunit is superimposed. b, comparison of the complexes formed by HPV-18 E2/D (gold) and BPV-1 E2/D (blue) with E2BS(AATT). The left subunit of each protein is superimposed. c, the intersubunit interactions between side chains in the [2]/ [3] loop and the C-terminal region of the recognition helix in the BPV-1 E2/D-E2BS(AATT) complex. The backbone worm representing relevant regions of the two subunits are shown in different colors.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 31245-31254) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20223699 A.G.Coyne, D.E.Scott, and C.Abell (2010).
Drugging challenging targets using fragment-based approaches.
  Curr Opin Chem Biol, 14, 299-307.  
20466807 M.van Dijk, and A.M.Bonvin (2010).
Pushing the limits of what is achievable in protein-DNA docking: benchmarking HADDOCK's performance.
  Nucleic Acids Res, 38, 5634-5647.  
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.  
20185566 Z.Xi, Y.Zhang, R.S.Hegde, Z.Shakked, and D.M.Crothers (2010).
Anomalous DNA binding by E2 regulatory protein driven by spacer sequence TATA.
  Nucleic Acids Res, 38, 3827-3833.  
19156829 D.E.Wetzler, M.Gallo, R.Melis, T.Eliseo, A.D.Nadra, D.U.Ferreiro, M.Paci, I.E.Sánchez, D.O.Cicero, and G.de Prat Gay (2009).
A strained DNA binding helix is conserved for site recognition, folding nucleation, and conformational modulation.
  Biopolymers, 91, 432-443.  
18664582 D.U.Ferreiro, I.E.Sánchez, and G.de Prat Gay (2008).
Transition state for protein-DNA recognition.
  Proc Natl Acad Sci U S A, 105, 10797-10802.  
18084026 I.E.Sánchez, M.Dellarole, K.Gaston, and G.de Prat Gay (2008).
Comprehensive comparison of the interaction of the E2 master regulator with its cognate target DNA sites in 73 human papillomavirus types by sequence statistics.
  Nucleic Acids Res, 36, 756-769.  
18287117 J.Curuksu, K.Zakrzewska, and M.Zacharias (2008).
Magnitude and direction of DNA bending induced by screw-axis orientation: influence of sequence, mismatches and abasic sites.
  Nucleic Acids Res, 36, 2268-2283.  
18487311 M.Falconi, F.Oteri, T.Eliseo, D.O.Cicero, and A.Desideri (2008).
MD simulations of papillomavirus DNA-E2 protein complexes hints at a protein structural code for DNA deformation.
  Biophys J, 95, 1108-1117.  
18515839 M.Gao, and J.Skolnick (2008).
DBD-Hunter: a knowledge-based method for the prediction of DNA-protein interactions.
  Nucleic Acids Res, 36, 3978-3992.  
17097712 K.Klucevsek, M.Wertz, J.Lucchi, A.Leszczynski, and J.Moroianu (2007).
Characterization of the nuclear localization signal of high risk HPV16 E2 protein.
  Virology, 360, 191-198.  
17350094 S.E.Lindner, and B.Sugden (2007).
The plasmid replicon of Epstein-Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells.
  Plasmid, 58, 1.  
16287204 C.M.Hebner, and L.A.Laimins (2006).
Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity.
  Rev Med Virol, 16, 83-97.  
16914454 E.Hooley, V.Fairweather, A.R.Clarke, K.Gaston, and R.L.Brady (2006).
The recognition of local DNA conformation by the human papillomavirus type 6 E2 protein.
  Nucleic Acids Res, 34, 3897-3908.
PDB codes: 2ayb 2aye 2ayg
16055534 D.Djuranovic, and B.Hartmann (2005).
Molecular dynamics studies on free and bound targets of the bovine papillomavirus type I e2 protein: the protein binding effect on DNA and the recognition mechanism.
  Biophys J, 89, 2542-2551.  
16216581 R.Rohs, H.Sklenar, and Z.Shakked (2005).
Structural and energetic origins of sequence-specific DNA bending: Monte Carlo simulations of papillomavirus E2-DNA binding sites.
  Structure, 13, 1499-1509.  
15942026 T.J.Su, M.R.Tock, S.U.Egelhaaf, W.C.Poon, and D.T.Dryden (2005).
DNA bending by M.EcoKI methyltransferase is coupled to nucleotide flipping.
  Nucleic Acids Res, 33, 3235-3244.  
14755573 K.S.Byun, and D.L.Beveridge (2004).
Molecular dynamics simulations of papilloma virus E2 DNA sequences: dynamical models for oligonucleotide structures in solution.
  Biopolymers, 73, 369-379.  
15148366 Y.Zhang, Z.Xi, R.S.Hegde, Z.Shakked, and D.M.Crothers (2004).
Predicting indirect readout effects in protein-DNA interactions.
  Proc Natl Acad Sci U S A, 101, 8337-8341.  
12930964 J.M.Zimmerman, and L.J.Maher (2003).
Solution measurement of DNA curvature in papillomavirus E2 binding sites.
  Nucleic Acids Res, 31, 5134-5139.  
12582248 T.D.Schaal, W.G.Mallet, D.L.McMinn, N.V.Nguyen, M.M.Sopko, S.John, and B.S.Parekh (2003).
Inhibition of human papilloma virus E2 DNA binding protein by covalently linked polyamides.
  Nucleic Acids Res, 31, 1282-1291.  
12352954 A.E.Maris, M.R.Sawaya, M.Kaczor-Grzeskowiak, M.R.Jarvis, S.M.Bearson, M.L.Kopka, I.Schröder, R.P.Gunsalus, and R.E.Dickerson (2002).
Dimerization allows DNA target site recognition by the NarL response regulator.
  Nat Struct Biol, 9, 771-778.
PDB code: 1je8
11988474 R.S.Hegde (2002).
The papillomavirus E2 proteins: structure, function, and biology.
  Annu Rev Biophys Biomol Struct, 31, 343-360.  
11160670 C.D.Newhouse, and S.J.Silverstein (2001).
Orientation of a novel DNA binding site affects human papillomavirus-mediated transcription and replication.
  J Virol, 75, 1722-1735.  
11438706 J.Hizver, H.Rozenberg, F.Frolow, D.Rabinovich, and Z.Shakked (2001).
DNA bending by an adenine--thymine tract and its role in gene regulation.
  Proc Natl Acad Sci U S A, 98, 8490-8495.
PDB code: 1ilc
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.

 

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