PDBsum entry 1g2d

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protein dna_rna metals links
Transcription/DNA PDB id
Jmol PyMol
Protein chains
89 a.a. *
_ZN ×6
Waters ×224
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Structure of a cys2his2 zinc finger/tata box complex (clone #2)
Structure: 5'- d( Gp Ap Cp Gp Cp Tp Ap Tp Ap Ap Ap Ap Gp Gp Ap G)-3'. Chain: a, d. Engineered: yes. 5'- d( Tp Cp Cp Tp Tp Tp Tp Ap Tp Ap Gp Cp Gp Tp Cp C)-3'. Chain: b, e. Engineered: yes. Tata box zinc finger protein.
Source: Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Other_details: protein selected by phage display.
Biol. unit: Trimer (from PQS)
2.20Å     R-factor:   0.225     R-free:   0.262
Authors: S.A.Wolfe,R.A.Grant,M.Elrod-Erickson,C.O.Pabo
Key ref:
S.A.Wolfe et al. (2001). Beyond the "recognition code": structures of two Cys2His2 zinc finger/TATA box complexes. Structure, 9, 717-723. PubMed id: 11587646 DOI: 10.1016/S0969-2126(01)00632-3
18-Oct-00     Release date:   07-Sep-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08046  (EGR1_MOUSE) -  Early growth response protein 1
533 a.a.
89 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 18 residue positions (black crosses)


DOI no: 10.1016/S0969-2126(01)00632-3 Structure 9:717-723 (2001)
PubMed id: 11587646  
Beyond the "recognition code": structures of two Cys2His2 zinc finger/TATA box complexes.
S.A.Wolfe, R.A.Grant, M.Elrod-Erickson, C.O.Pabo.
BACKGROUND: Several methods have been developed for creating Cys2His2 zinc finger proteins that recognize novel DNA sequences, and these proteins may have important applications in biological research and gene therapy. In spite of this progress with design/selection methodology, fundamental questions remain about the principles that govern DNA recognition. One hypothesis suggests that recognition can be described by a simple set of rules--essentially a "recognition code"--but careful assessment of this proposal has been difficult because there have been few structural studies of selected zinc finger proteins. RESULTS: We report the high-resolution cocrystal structures of two zinc finger proteins that had been selected (as variants of Zif268) to recognize a eukaryotic TATA box sequence. The overall docking arrangement of the fingers within the major groove of the DNA is similar to that observed in the Zif268 complex. Nevertheless, comparison of Zif268 and the selected variants reveal significant differences in the pattern of side chain-base interactions. The new structures also reveal side chain-side chain interactions (both within and between fingers) that are important in stabilizing the protein-DNA interface and appear to play substantial roles in recognition. CONCLUSIONS: These new structures highlight the surprising complexity of zinc finger-DNA interactions. The diversity of interactions observed at the protein-DNA interface, which is especially striking for proteins that were all derived from Zif268, challenges fundamental concepts about zinc finger-DNA recognition and underscores the difficulty in developing any meaningful recognition code.
  Selected figure(s)  
Figure 4.
Figure 4. Side Chain-Side Chain Interactions within the Recognition Helix Stabilize the Protein-DNA InterfaceIn the selected TATA proteins, whenever glutamine was present at position 6 of finger 2, threonine was absolutely conserved at position 2 [7]. The structure of TATA[ZF]* explains this preference; the g-methyl group of Thr-48 and the methyl group of T8 pack against opposite faces of Gln-52. Presumably, this stabilizes the interaction of Gln-52 with A7. This is analogous to the interfinger interaction described between fingers 1 and 2 of TATA[ZF] in Figure 3a. (Coloring scheme is the same as in Figure 2.)

  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 717-723) copyright 2001.  
  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.  
21207099 Z.Xie, S.Hu, J.Qian, S.Blackshaw, and H.Zhu (2011).
Systematic characterization of protein-DNA interactions.
  Cell Mol Life Sci, 68, 1657-1668.  
20594338 D.Davis, and D.Stokoe (2010).
Zinc Finger Nucleases as tools to understand and treat human diseases.
  BMC Med, 8, 42.  
20044539 F.Baudat, J.Buard, C.Grey, A.Fledel-Alon, C.Ober, M.Przeworski, G.Coop, and Massy (2010).
PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.
  Science, 327, 836-840.  
20717154 F.D.Urnov, E.J.Rebar, M.C.Holmes, H.S.Zhang, and P.D.Gregory (2010).
Genome editing with engineered zinc finger nucleases.
  Nat Rev Genet, 11, 636-646.  
19008249 A.V.Persikov, R.Osada, and M.Singh (2009).
Predicting DNA recognition by Cys2His2 zinc finger proteins.
  Bioinformatics, 25, 22-29.  
19198653 J.E.Foley, J.R.Yeh, M.L.Maeder, D.Reyon, J.D.Sander, R.T.Peterson, and J.K.Joung (2009).
Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN).
  PLoS ONE, 4, e4348.  
19798082 M.L.Maeder, S.Thibodeau-Beganny, J.D.Sander, D.F.Voytas, and J.K.Joung (2009).
Oligomerized pool engineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays.
  Nat Protoc, 4, 1471-1501.  
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.  
18328744 A.Zarebski, C.S.Velu, A.M.Baktula, T.Bourdeau, S.R.Horman, S.Basu, S.J.Bertolone, M.Horwitz, D.A.Hildeman, J.O.Trent, and H.L.Grimes (2008).
Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1.
  Immunity, 28, 370-380.  
19081059 E.J.Little, A.C.Babic, and N.C.Horton (2008).
Early interrogation and recognition of DNA sequence by indirect readout.
  Structure, 16, 1828-1837.
PDB code: 3ebc
18586699 J.Liu, and G.D.Stormo (2008).
Context-dependent DNA recognition code for C2H2 zinc-finger transcription factors.
  Bioinformatics, 24, 1850-1857.  
18585359 M.F.Berger, G.Badis, A.R.Gehrke, S.Talukder, A.A.Philippakis, L.Peña-Castillo, T.M.Alleyne, S.Mnaimneh, O.B.Botvinnik, E.T.Chan, F.Khalid, W.Zhang, D.Newburger, S.A.Jaeger, Q.D.Morris, M.L.Bulyk, and T.R.Hughes (2008).
Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences.
  Cell, 133, 1266-1276.  
18657511 M.L.Maeder, S.Thibodeau-Beganny, A.Osiak, D.A.Wright, R.M.Anthony, M.Eichtinger, T.Jiang, J.E.Foley, R.J.Winfrey, J.A.Townsend, E.Unger-Wallace, J.D.Sander, F.Müller-Lerch, F.Fu, J.Pearlberg, C.Göbel, J.P.Dassie, S.M.Pruett-Miller, M.H.Porteus, D.C.Sgroi, A.J.Iafrate, D.Dobbs, P.B.McCray, T.Cathomen, D.F.Voytas, and J.K.Joung (2008).
Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification.
  Mol Cell, 31, 294-301.  
18545224 T.Cathomen, and J.K.Joung (2008).
Zinc-finger nucleases: the next generation emerges.
  Mol Ther, 16, 1200-1207.  
18410495 Y.Zheng, J.Kief, K.Auffarth, J.W.Farfsing, M.Mahlert, F.Nieto, and C.W.Basse (2008).
The Ustilago maydis Cys2His2-type zinc finger transcription factor Mzr1 regulates fungal gene expression during the biotrophic growth stage.
  Mol Microbiol, 68, 1450-1470.  
16865673 N.P.Mongan, K.M.Martin, and L.J.Gudas (2006).
The putative human stem cell marker, Rex-1 (Zfp42): structural classification and expression in normal human epithelial and carcinoma cell cultures.
  Mol Carcinog, 45, 887-900.  
16906878 R.G.Endres, and N.S.Wingreen (2006).
Weight matrices for protein-DNA binding sites from a single co-crystal structure.
  Phys Rev E Stat Nonlin Soft Matter Phys, 73, 061921.  
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.  
  16511099 J.W.Crotty, C.Etzkorn, C.F.Barbas, D.J.Segal, and N.C.Horton (2005).
Crystallization and preliminary X-ray crystallographic analysis of Aart, a designed six-finger zinc-finger peptide, bound to DNA.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 573-576.  
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.  
14725771 G.Paillard, and R.Lavery (2004).
Analyzing protein-DNA recognition mechanisms.
  Structure, 12, 113-122.  
12620233 A.S.McCarty, G.Kleiger, D.Eisenberg, and S.T.Smale (2003).
Selective dimerization of a C2H2 zinc finger subfamily.
  Mol Cell, 11, 459-470.  
12667874 D.J.Segal, J.T.Stege, and C.F.Barbas (2003).
Zinc fingers and a green thumb: manipulating gene expression in plants.
  Curr Opin Plant Biol, 6, 163-168.  
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
12804117 H.R.Chrisman, and D.J.Tindall (2003).
Identification and characterization of a consensus DNA binding element for the zinc finger transcription factor TIEG/EGRalpha.
  DNA Cell Biol, 22, 187-199.  
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.  
12736264 R.J.Simpson, E.D.Cram, R.Czolij, J.M.Matthews, M.Crossley, and J.P.Mackay (2003).
CCHX zinc finger derivatives retain the ability to bind Zn(II) and mediate protein-DNA interactions.
  J Biol Chem, 278, 28011-28018.
PDB code: 1p7a
11917033 L.A.Mirny, and M.S.Gelfand (2002).
Structural analysis of conserved base pairs in protein-DNA complexes.
  Nucleic Acids Res, 30, 1704-1711.  
12271125 X.Guan, J.Stege, M.Kim, Z.Dahmani, N.Fan, P.Heifetz, C.F.Barbas, and S.P.Briggs (2002).
Heritable endogenous gene regulation in plants with designed polydactyl zinc finger transcription factors.
  Proc Natl Acad Sci U S A, 99, 13296-13301.  
11849947 D.J.Segal, and C.F.Barbas (2001).
Custom DNA-binding proteins come of age: polydactyl zinc-finger proteins.
  Curr Opin Biotechnol, 12, 632-637.  
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 code is shown on the right.