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Transcription/DNA
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PDB id
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1a3q
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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nucleus
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1 term
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Biological process
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regulation of transcription
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2 terms
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Biochemical function
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transcription factor activity
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1 term
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DOI no:
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EMBO J
16:7078-7090
(1997)
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PubMed id:
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Structure of the human NF-kappaB p52 homodimer-DNA complex at 2.1 A resolution.
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P.Cramer,
C.J.Larson,
G.L.Verdine,
C.W.Müller.
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ABSTRACT
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The crystal structure of human NF-kappaB p52 in its specific complex with the
natural kappaB DNA binding site MHC H-2 has been solved at 2.1 A resolution.
Whereas the overall structure resembles that of the NF-kappaB p50-DNA complex,
pronounced differences are observed within the 'insert region'. This sequence
segment differs in length between different Rel proteins. Compared with
NF-kappaB p50, the compact alpha-helical insert region element is rotated away
from the core of the N-terminal domain, opening up a mainly polar cleft. The
insert region presents potential interaction surfaces to other proteins. The
high resolution of the structure reveals many water molecules which mediate
interactions in the protein-DNA interface. Additional complexity in Rel
protein-DNA interaction comes from an extended interfacial water cavity that
connects residues at the edge of the dimer interface to the central DNA bases.
The observed water network might acount for differences in binding specificity
between NF-kappaB p52 and NF-kappaB p50 homodimers.
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Selected figure(s)
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Figure 2.
Figure 2 (A) Overall view of the NF- B
p52 homodimer -DNA complex structure along the DNA helical axis
with the approximate dyad vertical. The DNA duplex is in blue.
Color coding for the protein is as in Figure 1A. Secondary
structure elements are labeled. DNA-contacting loops are labeled
for monomer I. The disordered loop HI is drawn as a dashed line.
(B) Stereo view of rearrangement of the N-terminal domains upon
DNA binding, based on superposition of the C-terminal domains of
both crystallographically independent monomers. The protein
chains are drawn as C -traces
(monomer I and II as thick and thin lines, respectively). The
view is approximately perpendicular to that in (A). The DNA is
shown in its relative position to monomer I. The -helices
A and B and the N- and C-termini are labeled. (C) Structural
comparison of the N-terminal domains of NF- B
p52 (yellow) and NF- B
p50 (green) based on superposition of C atoms
of the N-terminal domain core. The view is similar to that in
(B). The protein structures are represented as backbone traces.
The helices within the insert region are emphasized.
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Figure 5.
Figure 5 DNA recognition by the NF- B
p52 homodimer. (A) Schematic diagram of polar interactions
between protein and DNA. Contacts to DNA bases (yellow boxes),
to the DNA backbone (red boxes) and water-mediated contacts
(green boxes) in both half sites are shown. Water molecules are
depicted as green spheres. (B) Stereo view of DNA base-specific
recognition in the first half site. Protein residues and DNA
bases are drawn with filled and open bonds, respectively. Water
molecules are drawn as open spheres. DNA backbone atoms have
been omitted for clarity. Polar interactions are indicated as
broken lines.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1997,
16,
7078-7090)
copyright 1997.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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| |
PubMed id
|
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Reference
|
 |
|
|
|
 |
C.Zheng,
Q.Yin,
and
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(2011).
Structural studies of NF-κB signaling.
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| |
Cell Res, 21,
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B.Barré,
and
N.D.Perkins
(2010).
The Skp2 promoter integrates signaling through the NF-kappaB, p53, and Akt/GSK3beta pathways to regulate autophagy and apoptosis.
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| |
Mol Cell, 38,
524-538.
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 |
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|
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A.J.Fusco,
D.B.Huang,
D.Miller,
V.Y.Wang,
D.Vu,
and
G.Ghosh
(2009).
NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes.
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| |
EMBO Rep, 10,
152-159.
|
 |
|
|
|
|
 |
T.Huxford,
and
G.Ghosh
(2009).
A structural guide to proteins of the NF-kappaB signaling module.
|
| |
Cold Spring Harbor Perspect Biol, 1,
a000075.
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|
|
|
|
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C.Mura,
and
J.A.McCammon
(2008).
Molecular dynamics of a kappaB DNA element: base flipping via cross-strand intercalative stacking in a microsecond-scale simulation.
|
| |
Nucleic Acids Res, 36,
4941-4955.
|
 |
|
|
|
|
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S.Raza,
K.A.Robertson,
P.A.Lacaze,
D.Page,
A.J.Enright,
P.Ghazal,
and
T.C.Freeman
(2008).
A logic-based diagram of signalling pathways central to macrophage activation.
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| |
BMC Syst Biol, 2,
36.
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F.Spyrakis,
P.Cozzini,
C.Bertoli,
A.Marabotti,
G.E.Kellogg,
and
A.Mozzarelli
(2007).
Energetics of the protein-DNA-water interaction.
|
| |
BMC Struct Biol, 7,
4.
|
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|
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G.Qing,
Z.Qu,
and
G.Xiao
(2007).
Endoproteolytic processing of C-terminally truncated NF-kappaB2 precursors at kappaB-containing promoters.
|
| |
Proc Natl Acad Sci U S A, 104,
5324-5329.
|
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|
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A.Hoffmann,
G.Natoli,
and
G.Ghosh
(2006).
Transcriptional regulation via the NF-kappaB signaling module.
|
| |
Oncogene, 25,
6706-6716.
|
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|
|
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K.Schumm,
S.Rocha,
J.Caamano,
and
N.D.Perkins
(2006).
Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit.
|
| |
EMBO J, 25,
4820-4832.
|
 |
|
|
|
|
 |
A.S.Romanenkov,
A.A.Ustyugov,
T.S.Zatsepin,
A.A.Nikulova,
I.V.Kolesnikov,
V.G.Metelev,
T.S.Oretskaya,
and
E.A.Kubareva
(2005).
Analysis of DNA-protein interactions in complexes of transcription factor NF-kappaB with DNA.
|
| |
Biochemistry (Mosc), 70,
1212-1222.
|
 |
|
|
|
|
 |
D.B.Huang,
D.Vu,
and
G.Ghosh
(2005).
NF-kappaB RelB forms an intertwined homodimer.
|
| |
Structure, 13,
1365-1373.
|
 |
|
PDB codes:
|
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|
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R.Fagerlund,
L.Kinnunen,
M.Köhler,
I.Julkunen,
and
K.Melén
(2005).
NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4.
|
| |
J Biol Chem, 280,
15942-15951.
|
 |
|
|
|
|
 |
S.C.Sun,
and
S.Yamaoka
(2005).
Activation of NF-kappaB by HTLV-I and implications for cell transformation.
|
| |
Oncogene, 24,
5952-5964.
|
 |
|
|
|
|
 |
D.Angelov,
F.Lenouvel,
F.Hans,
C.W.Müller,
P.Bouvet,
J.Bednar,
E.N.Moudrianakis,
J.Cadet,
and
S.Dimitrov
(2004).
The histone octamer is invisible when NF-kappaB binds to the nucleosome.
|
| |
J Biol Chem, 279,
42374-42382.
|
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|
|
|
|
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G.Ghosh,
D.B.Huang,
and
T.Huxford
(2004).
Molecular mimicry of the NF-kappaB DNA target site by a selected RNA aptamer.
|
| |
Curr Opin Struct Biol, 14,
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|
 |
|
|
|
|
 |
G.Xiao,
A.Fong,
and
S.C.Sun
(2004).
Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation.
|
| |
J Biol Chem, 279,
30099-30105.
|
 |
|
|
|
|
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S.Cheek,
Y.Qi,
S.S.Krishna,
L.N.Kinch,
and
N.V.Grishin
(2004).
4SCOPmap: automated assignment of protein structures to evolutionary superfamilies.
|
| |
BMC Bioinformatics, 5,
197.
|
 |
|
|
|
|
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Z.Qu,
G.Qing,
A.Rabson,
and
G.Xiao
(2004).
Tax deregulation of NF-kappaB2 p100 processing involves both beta-TrCP-dependent and -independent mechanisms.
|
| |
J Biol Chem, 279,
44563-44572.
|
 |
|
|
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|
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A.Nijnik,
R.Mott,
D.P.Kwiatkowski,
and
I.A.Udalova
(2003).
Comparing the fine specificity of DNA binding by NF-kappaB p50 and p52 using principal coordinates analysis.
|
| |
Nucleic Acids Res, 31,
1497-1501.
|
 |
|
|
|
|
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B.Rayet,
Y.Fan,
and
C.Gélinas
(2003).
Mutations in the v-Rel transactivation domain indicate altered phosphorylation and identify a subset of NF-kappaB-regulated cell death inhibitors important for v-Rel transforming activity.
|
| |
Mol Cell Biol, 23,
1520-1533.
|
 |
|
|
|
|
 |
D.Angelov,
M.Charra,
C.W.Müller,
J.Cadet,
and
S.Dimitrov
(2003).
Solution study of the NF-kappaB p50-DNA complex by UV laser protein-DNA cross-linking.
|
| |
Photochem Photobiol, 77,
592-596.
|
 |
|
|
|
|
 |
D.B.Huang,
D.Vu,
L.A.Cassiday,
J.M.Zimmerman,
L.J.Maher,
and
G.Ghosh
(2003).
Crystal structure of NF-kappaB (p50)2 complexed to a high-affinity RNA aptamer.
|
| |
Proc Natl Acad Sci U S A, 100,
9268-9273.
|
 |
|
PDB code:
|
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|
 |
H.R.Mott,
D.Nietlispach,
L.J.Hopkins,
G.Mirey,
J.H.Camonis,
and
D.Owen
(2003).
Structure of the GTPase-binding domain of Sec5 and elucidation of its Ral binding site.
|
| |
J Biol Chem, 278,
17053-17059.
|
 |
|
PDB code:
|
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|
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A.S.Liss,
and
H.R.Bose
(2002).
Mutational analysis of the v-Rel dimerization interface reveals a critical role for v-Rel homodimers in transformation.
|
| |
J Virol, 76,
4928-4939.
|
 |
|
|
|
|
 |
B.Berkowitz,
D.B.Huang,
F.E.Chen-Park,
P.B.Sigler,
and
G.Ghosh
(2002).
The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the interferon beta -kappa B site.
|
| |
J Biol Chem, 277,
24694-24700.
|
 |
|
PDB codes:
|
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|
 |
C.R.Escalante,
L.Shen,
D.Thanos,
and
A.K.Aggarwal
(2002).
Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
|
| |
Structure, 10,
383-391.
|
 |
|
PDB code:
|
 |
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|
|
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|
 |
F.E.Chen-Park,
D.B.Huang,
B.Noro,
D.Thanos,
and
G.Ghosh
(2002).
The kappa B DNA sequence from the HIV long terminal repeat functions as an allosteric regulator of HIV transcription.
|
| |
J Biol Chem, 277,
24701-24708.
|
 |
|
PDB code:
|
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|
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J.C.Stroud,
C.Lopez-Rodriguez,
A.Rao,
and
L.Chen
(2002).
Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor.
|
| |
Nat Struct Biol, 9,
90-94.
|
 |
|
PDB code:
|
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|
 |
K.Wecker,
M.C.Bonnet,
E.F.Meurs,
and
M.Delepierre
(2002).
The role of the phosphorus BI-BII transition in protein-DNA recognition: the NF-kappaB complex.
|
| |
Nucleic Acids Res, 30,
4452-4459.
|
 |
|
|
|
|
 |
L.F.Onuchic,
L.Furu,
Y.Nagasawa,
X.Hou,
T.Eggermann,
Z.Ren,
C.Bergmann,
J.Senderek,
E.Esquivel,
R.Zeltner,
S.Rudnik-Schöneborn,
M.Mrug,
W.Sweeney,
E.D.Avner,
K.Zerres,
L.M.Guay-Woodford,
S.Somlo,
and
G.G.Germino
(2002).
PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.
|
| |
Am J Hum Genet, 70,
1305-1317.
|
 |
|
|
|
|
 |
R.E.Speight,
D.J.Hart,
and
J.M.Blackburn
(2002).
Distamycin A affects the stability of NF-kappaB p50-DNA complexes in a sequence-dependent manner.
|
| |
J Mol Recognit, 15,
19-26.
|
 |
|
|
|
|
 |
F.Michel,
M.Soler-Lopez,
C.Petosa,
P.Cramer,
U.Siebenlist,
and
C.W.Müller
(2001).
Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family.
|
| |
EMBO J, 20,
6180-6190.
|
 |
|
PDB codes:
|
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|
 |
G.Xiao,
M.E.Cvijic,
A.Fong,
E.W.Harhaj,
M.T.Uhlik,
M.Waterfield,
and
S.C.Sun
(2001).
Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.
|
| |
EMBO J, 20,
6805-6815.
|
 |
|
|
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|
 |
P.Hainaut,
and
K.Mann
(2001).
Zinc binding and redox control of p53 structure and function.
|
| |
Antioxid Redox Signal, 3,
611-623.
|
 |
|
|
|
|
 |
T.H.Tahirov,
T.Inoue-Bungo,
H.Morii,
A.Fujikawa,
M.Sasaki,
K.Kimura,
M.Shiina,
K.Sato,
T.Kumasaka,
M.Yamamoto,
S.Ishii,
and
K.Ogata
(2001).
Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta.
|
| |
Cell, 104,
755-767.
|
 |
|
PDB codes:
|
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|
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J.P.Menetski
(2000).
The structure of the nuclear factor-kappaB protein-DNA complex varies with DNA-binding site sequence.
|
| |
J Biol Chem, 275,
7619-7625.
|
 |
|
|
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|
 |
P.Cramer,
D.A.Bushnell,
J.Fu,
A.L.Gnatt,
B.Maier-Davis,
N.E.Thompson,
R.R.Burgess,
A.M.Edwards,
P.R.David,
and
R.D.Kornberg
(2000).
Architecture of RNA polymerase II and implications for the transcription mechanism.
|
| |
Science, 288,
640-649.
|
 |
|
PDB code:
|
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|
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Y.Q.Chen,
L.L.Sengchanthalangsy,
A.Hackett,
and
G.Ghosh
(2000).
NF-kappaB p65 (RelA) homodimer uses distinct mechanisms to recognize DNA targets.
|
| |
Structure, 8,
419-428.
|
 |
|
|
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|
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C.Mischiati,
M.Borgatti,
N.Bianchi,
C.Rutigliano,
M.Tomassetti,
G.Feriotto,
and
R.Gambari
(1999).
Interaction of the human NF-kappaB p52 transcription factor with DNA-PNA hybrids mimicking the NF-kappaB binding sites of the human immunodeficiency virus type 1 promoter.
|
| |
J Biol Chem, 274,
33114-33122.
|
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|
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|
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P.Cramer,
A.Varrot,
C.Barillas-Mury,
F.C.Kafatos,
and
C.W.Müller
(1999).
Structure of the specificity domain of the Dorsal homologue Gambif1 bound to DNA.
|
| |
Structure, 7,
841-852.
|
 |
|
PDB code:
|
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|
 |
P.Cramer,
and
C.W.Müller
(1999).
A firm hand on NFkappaB: structures of the IkappaBalpha-NFkappaB complex.
|
| |
Structure, 7,
R1-R6.
|
 |
|
|
|
|
 |
R.de Martin,
J.A.Schmid,
and
R.Hofer-Warbinek
(1999).
The NF-kappaB/Rel family of transcription factors in oncogenic transformation and apoptosis.
|
| |
Mutat Res, 437,
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|
 |
|
|
|
|
 |
S.G.Sedgwick,
and
S.J.Smerdon
(1999).
The ankyrin repeat: a diversity of interactions on a common structural framework.
|
| |
Trends Biochem Sci, 24,
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|
 |
|
|
|
|
 |
T.Huxford,
S.Malek,
and
G.Ghosh
(1999).
Structure and mechanism in NF-kappa B/I kappa B signaling.
|
| |
Cold Spring Harb Symp Quant Biol, 64,
533-540.
|
 |
|
|
|
|
 |
X.M.Zhang,
and
G.L.Verdine
(1999).
A small region in HMG I(Y) is critical for cooperation with NF-kappaB on DNA.
|
| |
J Biol Chem, 274,
20235-20243.
|
 |
|
|
|
|
 |
S.Becker,
B.Groner,
and
C.W.Müller
(1998).
Three-dimensional structure of the Stat3beta homodimer bound to DNA.
|
| |
Nature, 394,
145-151.
|
 |
|
PDB code:
|
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|
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S.Malek,
T.Huxford,
and
G.Ghosh
(1998).
Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB.
|
| |
J Biol Chem, 273,
25427-25435.
|
 |
|
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 |
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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|