PDBsum entry 1a1k

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protein dna_rna metals links
Transcription/DNA PDB id
Protein chain
85 a.a. *
_ZN ×3
Waters ×121
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Radr (zif268 variant) zinc finger-DNA complex (gacc site)
Structure: DNA (5'-d( Ap Gp Cp Gp Tp Gp Gp Gp Ap Cp C)-3'). Chain: b. Engineered: yes. DNA (5'-d( Tp Gp Gp Tp Cp Cp Cp Ap Cp Gp C)-3'). Chain: c. Engineered: yes. Radr zif268 variant. Chain: a. Fragment: zinc finger.
Source: Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.90Å     R-factor:   0.210     R-free:   0.259
Authors: M.Elrod-Erickson,T.E.Benson,C.O.Pabo
Key ref:
M.Elrod-Erickson et al. (1998). High-resolution structures of variant Zif268-DNA complexes: implications for understanding zinc finger-DNA recognition. Structure, 6, 451-464. PubMed id: 9562555 DOI: 10.1016/S0969-2126(98)00047-1
10-Dec-97     Release date:   10-Jun-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08046  (EGR1_MOUSE) -  Early growth response protein 1
533 a.a.
85 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleic acid binding     2 terms  


DOI no: 10.1016/S0969-2126(98)00047-1 Structure 6:451-464 (1998)
PubMed id: 9562555  
High-resolution structures of variant Zif268-DNA complexes: implications for understanding zinc finger-DNA recognition.
M.Elrod-Erickson, T.E.Benson, C.O.Pabo.
BACKGROUND: Zinc fingers of the Cys2-His2 class comprise one of the largest families of eukaryotic DNA-binding motifs and recognize a diverse set of DNA sequences. These proteins have a relatively simple modular structure and key base contacts are typically made by a few residues from each finger. These features make the zinc finger motif an attractive system for designing novel DNA-binding proteins and for exploring fundamental principles of protein-DNA recognition. RESULTS: Here we report the X-ray crystal structures of zinc finger-DNA complexes involving three variants of Zif268, with multiple changes in the recognition helix of finger one. We describe the structure of each of these three-finger peptides bound to its corresponding target site. To help elucidate the differential basis for site-specific recognition, the structures of four other complexes containing various combinations of these peptides with alternative binding sites have also been determined. CONCLUSIONS: The protein-DNA contacts observed in these complexes reveal the basis for the specificity demonstrated by these Zif268 variants. Many, but not all, of the contacts can be rationalized in terms of a recognition code, but the predictive value of such a code is limited. The structures illustrate how modest changes in the docking arrangement accommodate the new sidechain-base and sidechain-phosphate interactions. Such adaptations help explain the versatility of naturally occurring zinc finger proteins and their utility in design.
  Selected figure(s)  
Figure 4.
Figure 4. Stereo view of the contacts made by finger one in the complex between (a) the RADR peptide and the targeted GCAC binding site, (b) the RADR peptide and the wild-type GCGT binding site, (c) the RADR peptide and the GACC binding site, and (d) the wild-type Zif268 peptide and the GCAC binding site. The sidechains of residues 18, 20, 21 and 24 (positions -1, 2, 3 and 6 of the a helix) and the peptide backbone are shown in gold for the RADR peptide, with alternate conformations indicated in gray. The wild-type peptide is shown in magenta, with alternate conformations indicated in gray. Water molecules are represented as spheres; only those water molecules that mediate interactions between the peptide and base pairs 8-10 are shown. The DNA is color-coded by strand, with the primary strand in purple and the secondary strand in blue. Fingers two and three are not shown. (The figure was made with the program SETOR [30].)
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 451-464) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20658568 B.Yang, Y.Zhu, Y.Wang, and G.Chen (2011).
Interaction identification of Zif268 and TATA(ZF) proteins with GC-/AT-rich DNA sequence: A theoretical study.
  J Comput Chem, 32, 416-428.  
20478078 A.Klug (2010).
The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation.
  Q Rev Biophys, 43, 1.  
20192761 A.Klug (2010).
The discovery of zinc fingers and their applications in gene regulation and genome manipulation.
  Annu Rev Biochem, 79, 213-231.  
20435679 J.D.Sander, M.L.Maeder, D.Reyon, D.F.Voytas, J.K.Joung, and D.Dobbs (2010).
ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool.
  Nucleic Acids Res, 38, W462-W468.  
20665475 M.Bueno, N.A.Temiz, and C.J.Camacho (2010).
Novel modulation factor quantifies the role of water molecules in protein interactions.
  Proteins, 78, 3226-3234.  
19965883 N.A.Temiz, A.Trapp, O.A.Prokopyev, and C.J.Camacho (2010).
Optimization of minimum set of protein-DNA interactions: a quasi exact solution with minimum over-fitting.
  Bioinformatics, 26, 319-325.  
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.  
19008249 A.V.Persikov, R.Osada, and M.Singh (2009).
Predicting DNA recognition by Cys2His2 zinc finger proteins.
  Bioinformatics, 25, 22-29.  
19244617 J.W.Locasale, A.A.Napoli, S.Chen, H.M.Berman, and C.L.Lawson (2009).
Signatures of protein-DNA recognition in free DNA binding sites.
  J Mol Biol, 386, 1054-1065.
PDB codes: 1hq7 2b1b 2b1c 2b1d
19429892 N.A.Temiz, and C.J.Camacho (2009).
Experimentally based contact energies decode interactions responsible for protein-DNA affinity and the role of molecular waters at the binding interface.
  Nucleic Acids Res, 37, 4076-4088.  
19119423 R.O.Emerson, and J.H.Thomas (2009).
Adaptive evolution in zinc finger transcription factors.
  PLoS Genet, 5, e1000325.  
18366021 A.Marabotti, F.Spyrakis, A.Facchiano, P.Cozzini, S.Alberti, G.E.Kellogg, and A.Mozzarelli (2008).
Energy-based prediction of amino acid-nucleotide base recognition.
  J Comput Chem, 29, 1955-1969.  
18586699 J.Liu, and G.D.Stormo (2008).
Context-dependent DNA recognition code for C2H2 zinc-finger transcription factors.
  Bioinformatics, 24, 1850-1857.  
19368013 J.Shearer (2008).
Influence of sequential guanidinium methylation on the energetics of the guanidinium...guanine dimer and guanidinium...guanine...cytosine trimer: implications for the control of protein...DNA interactions by arginine methyltransferases.
  J Phys Chem B, 112, 16995-17002.  
17603475 J.C.Miller, M.C.Holmes, J.Wang, D.Y.Guschin, Y.L.Lee, I.Rupniewski, C.M.Beausejour, A.J.Waite, N.S.Wang, K.A.Kim, P.D.Gregory, C.O.Pabo, and E.J.Rebar (2007).
An improved zinc-finger nuclease architecture for highly specific genome editing.
  Nat Biotechnol, 25, 778-785.  
17264930 M.J.Hannon (2007).
Supramolecular DNA recognition.
  Chem Soc Rev, 36, 280-295.  
16829533 A.J.Bird, S.Swierczek, W.Qiao, D.J.Eide, and D.R.Winge (2006).
Zinc metalloregulation of the zinc finger pair domain.
  J Biol Chem, 281, 25326-25335.  
16548034 R.Zadmard, and T.Schrader (2006).
DNA recognition with large calixarene dimers.
  Angew Chem Int Ed Engl, 45, 2703-2706.  
16826557 S.H.Mishra, C.M.Shelley, D.J.Barrow, M.K.Darby, and M.W.Germann (2006).
Solution structures and characterization of human immunodeficiency virus Rev responsive element IIB RNA targeting zinc finger proteins.
  Biopolymers, 83, 352-364.
PDB codes: 2ab3 2ab7
16121397 D.Lejeune, N.Delsaux, B.Charloteaux, A.Thomas, and R.Brasseur (2005).
Protein-nucleic acid recognition: statistical analysis of atomic interactions and influence of DNA structure.
  Proteins, 61, 258-271.  
16014175 J.Liu, and G.D.Stormo (2005).
Quantitative analysis of EGR proteins binding to DNA: assessing additivity in both the binding site and the protein.
  BMC Bioinformatics, 6, 176.  
15830130 R.Holmes-Davis, G.Li, A.C.Jamieson, E.J.Rebar, Q.Liu, Y.Kong, C.C.Case, and P.D.Gregory (2005).
Gene regulation in planta by plant-derived engineered zinc finger protein transcription factors.
  Plant Mol Biol, 57, 411-423.  
16194281 T.J.Magliery, and L.Regan (2005).
Sequence variation in ligand binding sites in proteins.
  BMC Bioinformatics, 6, 240.  
16103898 T.Kaplan, N.Friedman, and H.Margalit (2005).
Ab initio prediction of transcription factor targets using structural knowledge.
  PLoS Comput Biol, 1, e1.  
14725771 G.Paillard, and R.Lavery (2004).
Analyzing protein-DNA recognition mechanisms.
  Structure, 12, 113-122.  
14652076 E.P.Baldwin, S.S.Martin, J.Abel, K.A.Gelato, H.Kim, P.G.Schultz, and S.W.Santoro (2003).
A specificity switch in selected cre recombinase variants is mediated by macromolecular plasticity and water.
  Chem Biol, 10, 1085-1094.
PDB codes: 1pvp 1pvq 1pvr
12592413 K.H.Bae, Y.D.Kwon, H.C.Shin, M.S.Hwang, E.H.Ryu, K.S.Park, H.Y.Yang, D.K.Lee, Y.Lee, J.Park, H.S.Kwon, H.W.Kim, B.I.Yeh, H.W.Lee, S.H.Sohn, J.Yoon, W.Seol, and J.S.Kim (2003).
Human zinc fingers as building blocks in the construction of artificial transcription factors.
  Nat Biotechnol, 21, 275-280.  
12761399 K.Koscielska-Kasprzak, T.Cierpicki, and J.Otlewski (2003).
Importance of alpha-helix N-capping motif in stabilization of betabetaalpha fold.
  Protein Sci, 12, 1283-1289.  
12923058 P.A.Reynolds, G.A.Smolen, R.E.Palmer, D.Sgroi, V.Yajnik, W.L.Gerald, and D.A.Haber (2003).
Identification of a DNA-binding site and transcriptional target for the EWS-WT1(+KTS) oncoprotein.
  Genes Dev, 17, 2094-2107.  
14621985 S.A.Wolfe, R.A.Grant, and C.O.Pabo (2003).
Structure of a designed dimeric zinc finger protein bound to DNA.
  Biochemistry, 42, 13401-13409.
PDB code: 1llm
12001270 P.V.Benos, A.S.Lapedes, and G.D.Stormo (2002).
Is there a code for protein-DNA recognition? Probab(ilistical)ly. . .
  Bioessays, 24, 466-475.  
11395410 C.O.Pabo, E.Peisach, and R.A.Grant (2001).
Design and selection of novel Cys2His2 zinc finger proteins.
  Annu Rev Biochem, 70, 313-340.  
11410653 T.K.Man, and G.D.Stormo (2001).
Non-independence of Mnt repressor-operator interaction determined by a new quantitative multiple fluorescence relative affinity (QuMFRA) assay.
  Nucleic Acids Res, 29, 2471-2478.  
10970879 B.S.Cobb, S.Morales-Alcelay, G.Kleiger, K.E.Brown, A.G.Fisher, and S.T.Smale (2000).
Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding.
  Genes Dev, 14, 2146-2160.  
10679372 D.J.Segal, and C.F.Barbas (2000).
Design of novel sequence-specific DNA-binding proteins.
  Curr Opin Chem Biol, 4, 34-39.  
10757987 M.Imanishi, Y.Hori, M.Nagaoka, and Y.Sugiura (2000).
DNA-bending finger: artificial design of 6-zinc finger peptides with polyglycine linker and induction of DNA bending.
  Biochemistry, 39, 4383-4390.  
10873713 M.Razmiafshari, and N.H.Zawia (2000).
Utilization of a synthetic peptide as a tool to study the interaction of heavy metals with the zinc finger domain of proteins critical for gene expression in the developing brain.
  Toxicol Appl Pharmacol, 166, 1.  
10940247 S.A.Wolfe, L.Nekludova, and C.O.Pabo (2000).
DNA recognition by Cys2His2 zinc finger proteins.
  Annu Rev Biophys Biomol Struct, 29, 183-212.  
10637336 S.Lee, and M.D.Garfinkel (2000).
Characterization of Drosophila OVO protein DNA binding specificity using random DNA oligomer selection suggests zinc finger degeneration.
  Nucleic Acids Res, 28, 826-834.  
11003663 V.Dave, C.Zhao, F.Yang, C.S.Tung, and J.Ma (2000).
Reprogrammable recognition codes in bicoid homeodomain-DNA interaction.
  Mol Cell Biol, 20, 7673-7684.  
10981627 Y.Choo, and M.Isalan (2000).
Advances in zinc finger engineering.
  Curr Opin Struct Biol, 10, 411-416.  
10077584 D.J.Segal, B.Dreier, R.R.Beerli, and C.F.Barbas (1999).
Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences.
  Proc Natl Acad Sci U S A, 96, 2758-2763.  
10685047 G.S.Beligere, and P.E.Dawson (1999).
Synthesis of a three zinc finger protein, Zif268, by native chemical ligation.
  Biopolymers, 51, 363-369.  
10383437 M.Elrod-Erickson, and C.O.Pabo (1999).
Binding studies with mutants of Zif268. Contribution of individual side chains to binding affinity and specificity in the Zif268 zinc finger-DNA complex.
  J Biol Chem, 274, 19281-19285.  
10421761 P.Blancafort, S.V.Steinberg, B.Paquin, R.Klinck, J.K.Scott, and R.Cedergren (1999).
The recognition of a noncanonical RNA base pair by a zinc finger protein.
  Chem Biol, 6, 585-597.  
10449375 R.W.Roberts, and W.W.Ja (1999).
In vitro selection of nucleic acids and proteins: What are we learning?
  Curr Opin Struct Biol, 9, 521-529.  
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.