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PDBsum entry 1a1h
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Transcription/DNA
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PDB id
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1a1h
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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High-Resolution structures of variant zif268-Dna complexes: implications for understanding zinc finger-Dna recognition.
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Authors
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M.Elrod-Erickson,
T.E.Benson,
C.O.Pabo.
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Ref.
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Structure, 1998,
6,
451-464.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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].)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
451-464)
copyright 1998.
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Secondary reference #1
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Title
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Zif268 protein-Dna complex refined at 1.6 a: a model system for understanding zinc finger-Dna interactions.
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Authors
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M.Elrod-Erickson,
M.A.Rould,
L.Nekludova,
C.O.Pabo.
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Ref.
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Structure, 1996,
4,
1171-1180.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. Overview of the Zif268-DNA complex, showing the
side chains that make direct base contacts. The peptide is
color-coded by finger: finger one is red, finger two is yellow,
and finger three is purple. The DNA is shown in dark blue, and
the zinc ions in pale blue.
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The above figure is
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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Zinc finger phage: affinity selection of fingers with new DNA-Binding specificities.
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Authors
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E.J.Rebar,
C.O.Pabo.
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Ref.
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Science, 1994,
263,
671-673.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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Zinc finger-Dna recognition: crystal structure of a zif268-Dna complex at 2.1 a.
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Authors
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N.P.Pavletich,
C.O.Pabo.
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Ref.
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Science, 1991,
252,
809-817.
[DOI no: ]
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PubMed id
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