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PDBsum entry 1qrv
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Gene regulation/DNA
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PDB id
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1qrv
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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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The structure of a chromosomal high mobility group protein-Dna complex reveals sequence-Neutral mechanisms important for non-Sequence-Specific DNA recognition.
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Authors
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F.V.Murphy,
R.M.Sweet,
M.E.Churchill.
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Ref.
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EMBO J, 1999,
18,
6610-6618.
[DOI no: ]
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PubMed id
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Abstract
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The high mobility group (HMG) chromosomal proteins, which are common to all
eukaryotes, bind DNA in a non-sequence-specific fashion to promote chromatin
function and gene regulation. They interact directly with nucleosomes and are
believed to be modulators of chromatin structure. They are also important in
V(D)J recombination and in activating a number of regulators of gene expression,
including p53, Hox transcription factors and steroid hormone receptors, by
increasing their affinity for DNA. The X-ray crystal structure, at 2.2 A
resolution, of the HMG domain of the Drosophila melanogaster protein, HMG-D,
bound to DNA provides the first detailed view of a chromosomal HMG domain
interacting with linear DNA and reveals the molecular basis of
non-sequence-specific DNA recognition. Ser10 forms water-mediated hydrogen bonds
to DNA bases, and Val32 with Thr33 partially intercalates the DNA. These two
'sequence-neutral' mechanisms of DNA binding substitute for base-specific
hydrogen bonds made by equivalent residues of the sequence-specific HMG domain
protein, lymphoid enhancer factor-1. The use of multiple intercalations and
water-mediated DNA contacts may prove to be generally important mechanisms by
which chromosomal proteins bind to DNA in the minor groove.
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Figure 1.
Figure 1 Structure of the HMG-box of HMG-D bound to DNA. (A)
Sequence comparison of sequence-specific and
non-sequence-specific HMG domains. The sequences are aligned and
numbered according to the HMG-D structure, with helices, I, II
and II depicted by black boxes (Jones et al., 1994; Baxevanis
and Landsman, 1995). Residues shown from structural and modeling
studies to intercalate the DNA are outlined in black (Love et
al., 1995; Werner et al., 1995a,b; Balaeff et al., 1998; Allain
et al., 1999; Ohndorf et al., 1999). Residues that are conserved
between the two HMG-box families are shaded in gray, whereas
those residues that consistently differ between the two families
of HMG domains are highlighted in cyan and brown (Balaeff et
al., 1998; Churchill et al., 1999). (B) Stereo view of the
refined (2|F[o]| - |F[c]|) electron density map contoured at a
level of 1.9  .
The protein and DNA are colored using standard CPK coloring,
with water molecules and a sodium ion represented by red and
blue spheres, respectively. (C) Ribbon diagram in stereo view of
the complex. HMG-D is depicted in cyan, the DNA in gray, and
structural water molecules found in the protein and at the DNA
interface in red. Several side chains that interact with the
DNA, Ser10, Tyr12, Met13, Asn17, Arg20, Val32, Thr33 and Ala36,
are shown in green. The protein is well ordered from residue 4
to 72, and the DNA is well ordered throughout except for base
cytosine 10, which adopts two conformations in the crystal (only
one conformation is shown).
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Figure 3.
Figure 3 Structural features involved in non-sequence-specific
DNA recognition. (A) View of HMG-D protein from this structure
(cyan) superimposed on the structure of the LEF-1 -DNA complex
(Love et al., 1995) (PDB accession No. 2lef; coral) in the same
orientation as Figure 1C. Side chains, selected on the basis of
their potential involvement in DNA specificity, are shown.
Detailed view of the interaction of residue 10 from both HMG-D
(B) and LEF-1 (C). HMG-D protein is in cyan, LEF-1 protein is in
coral, DNA is in gray, and black dashed lines depict proposed
hydrogen bonds with distances between donors and acceptors
shown. The Ser10 hydroxyl oxygen of HMG-D makes water-mediated
interactions with adenine 6 N3 and thymine 7 O4'. The LEF-1
Asn10 makes direct hydrogen bonds to guanine 9 N3 and thymine 8
O2 (in this LEF-1 model).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
6610-6618)
copyright 1999.
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