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PDBsum entry 1bft
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Transcription factor
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PDB id
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1bft
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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 role of DNA in the mechanism of nfkappab dimer formation: crystal structures of the dimerization domains of the p50 and p65 subunits.
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Authors
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D.B.Huang,
T.Huxford,
Y.Q.Chen,
G.Ghosh.
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Ref.
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Structure, 1997,
5,
1427-1436.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Members of the rel/NFkappaB family of transcription factors play a
vital role in the regulation of rapid cellular responses, such as those required
to fight infection or react to cellular stress. Members of this family of
proteins form homo- and heterodimers with differing affinities for dimerization.
They share a structural motif known as the rel homology region (RHR), the
C-terminal one third of which mediates protein dimerization. Crystal structures
of the rel/NFkappaB family members p50 and p65 in their DNA-bound homodimeric
form have been solved. These structures showed that the residues from the
dimerization domains of both p50 and p65 participate in DNA binding and that the
DNA-protein and protein dimerization surfaces form one continuous overlapping
interface. We desired to investigate the contribution of DNA to NFkappaB
dimerization and to identify the mechanism for the selective association of
rel/NFkappaB family peptides into transcriptionally active dimers. RESULTS: We
report here the crystal structures of the dimerization domains of murine p50 and
p65 at 2.2 A and 2.0 A resolution, respectively. A comparison of these two
structures suggests that conservative amino acid changes at three positions are
responsible for the differences in their dimer interfaces. The presence of the
target DNA does not change the dimer interface of either protein in any
significant manner. CONCLUSIONS: These two structures suggest that the
rel/NFkappaB family of transcription factors use only a few conservative changes
in their amino acid sequences to form a host of dimers with varying affinities
for dimerization. Amino acids at positions corresponding to 254, 267, and 307 of
murine p50, function as primary determinants for the observed differences in
dimerization affinity. The DNA-contacting charged amino acid sidechains from the
dimerization domains are held in a similar conformation in both the DNA-bound
and free states, therefore, no major structural rearrangement is required to
bring these residues into contact with the DNA.
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Figure 2.
Figure 2. Comparison of the contribution of residues Tyr267
and Asp254 of p50 and the homologous pair, Phe213 and Asn200 of
p65, to their respective dimer interfaces. The different
monomers are indicated by the letters A and B preceding the
amino acid number. (a) In p50, Tyr267 from monomer A (cyan) and
monomer B (green) participate in hydrogen-bonding networks (red
dashed lines) which direct the two Asp254 residues towards each
other in a dimer-weakening interaction. (b) In p65, the two
Phe213 residues fail to form the extensive hydrogen-bonding
networks of the homologous Tyr267 in p50. The weaker dimer
interface allows the polar Asn200 residues of monomer A (cyan)
and B (green) the freedom to move away from each other.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
1427-1436)
copyright 1997.
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Secondary reference #1
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Title
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Structure of nf-Kappa b p50 homodimer bound to a kappa b site.
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Authors
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G.Ghosh,
G.Van duyne,
S.Ghosh,
P.B.Sigler.
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Ref.
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Nature, 1995,
373,
303-310.
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PubMed id
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