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PDBsum entry 2r5z
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Transcription/DNA
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PDB id
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2r5z
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References listed in PDB file
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Key reference
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Title
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Functional specificity of a hox protein mediated by the recognition of minor groove structure.
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Authors
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R.Joshi,
J.M.Passner,
R.Rohs,
R.Jain,
A.Sosinsky,
M.A.Crickmore,
V.Jacob,
A.K.Aggarwal,
B.Honig,
R.S.Mann.
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Ref.
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Cell, 2007,
131,
530-543.
[DOI no: ]
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PubMed id
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Abstract
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The recognition of specific DNA-binding sites by transcription factors is a
critical yet poorly understood step in the control of gene expression. Members
of the Hox family of transcription factors bind DNA by making nearly identical
major groove contacts via the recognition helices of their homeodomains. In vivo
specificity, however, often depends on extended and unstructured regions that
link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a
combination of structure determination, computational analysis, and in vitro and
in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding
sites via residues located in these extended regions that insert into the minor
groove but only when presented with the correct DNA sequence. Our results
suggest that these residues, which are conserved in a paralog-specific manner,
confer specificity by recognizing a sequence-dependent DNA structure instead of
directly reading a specific DNA sequence.
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Figure 2.
Figure 2. Protein-DNA Contacts
Protein-DNA contacts for
the (A) fkh250 and (B) fkh250^con* complexes. The Exd half site
is shaded cyan, the Hox half site is shaded red. Hydrogen bonds
are represented by solid lines and nonpolar interactions by
dotted lines. Interactions involving the protein main chain are
underlined. Green circles are visualized water molecules. The
fkh250 complex has more water-mediated contacts from residues
such as Gln50, which is oriented differently in the two
complexes, and Trp-17, which is positioned identically in the
two complexes.
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Figure 3.
Figure 3. Minor Groove Insertion of Scr Residues His−12 and
Arg3 in fkh250
(A) Electron densities for Arg3 and His−12
in the fkh250 complex, based on a simulated annealing Fo-Fc omit
map (contoured at 3.0σ).
(B) Details of the
His−12–Arg3 interaction and water-mediated interactions with
Thy14, Thy29, and Thy30 of fkh250. The red circle marks a water
molecule and dotted lines represent putative hydrogen bonds.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Cell
(2007,
131,
530-543)
copyright 2007.
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