PDBsum entry: 1a1k

Transcription/DNA

PDB-id

1a1k


	Main view

Contents

Description

Header details

Protein chain

DNA/RNA

Metal ions

_ZN ×3

Waters ×121

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation


Right view		Bottom view

PDB id:

1a1k

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.

UniProt:

P08046 (EGR1_MOUSE)

Seq:

Struc:

Seq:

Struc:

Seq:

533 a.a.

Struc:

85 a.a.*

Key:		PfamA domain			PfamB domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Resolution:

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]

Date:

10-Dec-97

Release date:

10-Jun-98

Quick_links

RCSB

PDBe

NDB

SRS

MMDB

JenaLib

OCA

PDBWiki

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

PQS

ProSAT

Whatcheck

Procheck

Clefts

Surface

Key reference

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.

ABSTRACT

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 the author.

Literature references that cite this PDB file's key reference

PubMed id Reference

19008249 A.V.Persikov, R.Osada, and M.Singh (2009).
Predicting DNA recognition by Cys2His2 zinc finger proteins.

Bioinformatics, 25, 22-29.

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.

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.

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.

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.

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.

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.

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.