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PDBsum entry 1vkx
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Transcription/DNA
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PDB id
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1vkx
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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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Crystal structure of p50/p65 heterodimer of transcription factor nf-Kappab bound to DNA.
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Authors
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F.E.Chen,
D.B.Huang,
Y.Q.Chen,
G.Ghosh.
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Ref.
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Nature, 1998,
391,
410-413.
[DOI no: ]
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PubMed id
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Abstract
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The NF-kappaB p50/p65 heterodimer is the classical member of the Rel family of
transcription factors which regulate diverse cellular functions such as immune
response, cell growth, and development. Other mammalian Rel family members,
including the proteins p52, proto-oncoprotein c-Rel, and RelB, all have
amino-terminal Rel-homology regions (RHRs). The RHR is responsible for the
dimerization, DNA binding and cytosolic localization of these proteins by virtue
of complex formation with inhibitor kappaB proteins. Signal-induced removal of
kappaB inhibitors allows translocation of dimers to the cell nucleus and
transcriptional regulation of kappaB DNA-containing genes. NF-kappaB
specifically recognizes kappaB DNA elements with a consensus sequence of
5'-GGGRNYYYCC-3' (R is an unspecified purine; Y is an unspecified pyrimidine;
and N is any nucleotide). Here we report the crystal structure at 2.9 A
resolution of the p50/p65 heterodimer bound to the kappaB DNA of the intronic
enhancer of the immunoglobulin light-chain gene. Our structure reveals a
5-base-pair 5' subsite for p50, and a 4-base-pair 3' subsite for p65. This
structure indicates why the p50/p65 heterodimer interface is stronger than that
of either homodimer. A comparison of this structure with those of other Rel
dimers reveals that both subunits adopt variable conformations in a
DNA-sequence-dependent manner. Our results explain the different behaviour of
the p50/p65 heterodimer with heterologous promoters.
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Figure 2.
Figure 2 The structure of the heterodimer bound on the Ig
 B
DNA. a, Ribbon drawing of the entire complex viewed down the DNA
helical axis. The p50 subunit is in green and the p65 subunit is
in red. The top strand of DNA is in pink, and the bottom strand
is in yellow. Drawing produced with SETOR30. b, The hydrophobic
core of the dimer interface between p50 (green) and p65 (red)
consists of an array of nonpolar hydrocarbons, aromatic rings
and uncharged polar residues pointing from the  -sheets
in towards the interface. Only the -strands
and seven residues contributing to the interface are displayed.
Oxygens (red) and nitrogens (dark blue) are included.
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Figure 3.
Figure 3 DNA contacts made by the heterodimer. a, The DNA
contacts made by the p50/p65 NF- B
heterodimer. Blue and green distinguish the p65 and the p50
subunits, respectively. Arrows denote hydrogen bonds; brown
ovals indicate van der Waals contacts. The p50 subunit binds to
the 5' five-base-pair subsite; the p65 subunit binds to the 3'
four-base-pair subsite. b (top), Stereo pair of the
base-specific interactions mediated by Arg 54, Arg 56, Glu 60
and His 64 of the p50 subunit. Hydrogen bonds are drawn as
dashed lines between grey oxygens and dark blue nitrogens. p50
residues are green, top strand bases are yellow, while the
bottom strand base is in blue. Bottom, Stereo pair of the
base-specific interactions mediated by Arg 34, Arg 35, Glu 39
and Arg 187 of the p65 subunit. p65 residues are shown in green.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
391,
410-413)
copyright 1998.
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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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