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PDBsum entry 1ram

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protein dna_rna ligands Protein-protein interface(s) links
Transcription/DNA PDB id
1ram
Jmol
Contents
Protein chains
273 a.a. *
DNA/RNA
Ligands
DTT ×2
Waters ×16
* Residue conservation analysis
PDB id:
1ram
Name: Transcription/DNA
Title: A novel DNA recognition mode by nf-kb p65 homodimer
Structure: DNA (5'- d( Cp Gp Gp Cp Tp Gp Gp Ap Ap Ap Tp Tp Tp Cp Cp Ap Gp Cp Cp G)-3'). Chain: c, d. Engineered: yes. Protein (transcription factor nf-kb p65). Chain: a, b. Fragment: p65 subunit, residues 19 - 291. Synonym: rela, nuclear factor kappa-b chain p65, avian
Source: Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.70Å     R-factor:   0.222     R-free:   0.324
Authors: Y.-Q.Chen,S.Ghosh,G.Ghosh
Key ref: Y.Q.Chen et al. (1998). A novel DNA recognition mode by the NF-kappa B p65 homodimer. Nat Struct Biol, 5, 67-73. PubMed id: 9437432
Date:
22-Nov-97     Release date:   27-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
Seq:
Struc:
 
Seq:
Struc:
549 a.a.
273 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     sequence-specific DNA binding transcription factor activity     1 term  

 

 
Nat Struct Biol 5:67-73 (1998)
PubMed id: 9437432  
 
 
A novel DNA recognition mode by the NF-kappa B p65 homodimer.
Y.Q.Chen, S.Ghosh, G.Ghosh.
 
  ABSTRACT  
 
The crystal structure of the NF-kappa B p65 (RelA) homodimer in complex with a DNA target has been determined to 2.4 A resolution. The two p65 subunits are not symmetrically disposed on the DNA target. The homodimer should optimally bind to a pseudo-palindromic nine base pair target with each subunit recognizing a 5'GGAA-3' half site separated by a central A-T base pair. However, one of the subunits (subunit B) encounters a half site of 5'-GAAA-3'. The single base-pair change from G-C to A-T results in highly unfavorable interactions between this half site and the base contacting protein residues in subunit B, which leads to an 18 degrees rotation of the N-terminal terminal domain from its normal conformation. Remarkably, subunit B retains all the interactions with the sugar phosphate backbone of the DNA target. This mode of interaction allows the NF-kappa B p65 homodimer to recognize DNA targets containing only one cognate half site. Differences in the sequence of the other half site provide variations in conformation and affinity of the complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472811 B.Manavalan, R.Govindaraj, G.Lee, and S.Choi (2011).
Molecular modeling-based evaluation of dual function of IκBζ ankyrin repeat domain in toll-like receptor signaling.
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21135870 C.Zheng, Q.Yin, and H.Wu (2011).
Structural studies of NF-κB signaling.
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21113130 K.Baruch, L.Gur-Arie, C.Nadler, S.Koby, G.Yerushalmi, Y.Ben-Neriah, O.Yogev, E.Shaulian, C.Guttman, R.Zarivach, and I.Rosenshine (2011).
Metalloprotease type III effectors that specifically cleave JNK and NF-κB.
  EMBO J, 30, 221-231.  
19098713 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.
  EMBO Rep, 10, 152-159.  
19201872 F.L.Sinquett, R.L.Dryer, V.Marcelli, A.Batheja, and L.R.Covey (2009).
Single nucleotide changes in the human Igamma1 and Igamma4 promoters underlie different transcriptional responses to CD40.
  J Immunol, 182, 2185-2193.  
19244617 J.W.Locasale, A.A.Napoli, S.Chen, H.M.Berman, and C.L.Lawson (2009).
Signatures of protein-DNA recognition in free DNA binding sites.
  J Mol Biol, 386, 1054-1065.
PDB codes: 1hq7 2b1b 2b1c 2b1d
19285436 K.Koga, G.Takaesu, R.Yoshida, M.Nakaya, T.Kobayashi, I.Kinjyo, and A.Yoshimura (2009).
Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein.
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19806632 L.Piccagli, E.Fabbri, M.Borgatti, N.Bianchi, V.Bezzerri, I.Mancini, E.Nicolis, C.M.Dechecchi, I.Lampronti, G.Cabrini, and R.Gambari (2009).
Virtual Screening against p50 NF-kappaB Transcription Factor for the Identification of Inhibitors of the NF-kappaB-DNA Interaction and Expression of NF-kappaB Upregulated Genes.
  ChemMedChem, 4, 2024-2033.  
  20066103 T.Huxford, and G.Ghosh (2009).
A structural guide to proteins of the NF-kappaB signaling module.
  Cold Spring Harbor Perspect Biol, 1, a000075.  
18462673 D.L.Bates, K.K.Barthel, Y.Wu, R.Kalhor, J.C.Stroud, M.J.Giffin, and L.Chen (2008).
Crystal structure of NFAT bound to the HIV-1 LTR tandem kappaB enhancer element.
  Structure, 16, 684-694.
PDB code: 2o93
18426920 S.E.Wurster, and L.J.Maher (2008).
Selection and characterization of anti-NF-kappaB p65 RNA aptamers.
  RNA, 14, 1037-1047.  
16760470 M.J.Schaaf, L.Willetts, B.P.Hayes, B.Maschera, E.Stylianou, and S.N.Farrow (2006).
The relationship between intranuclear mobility of the NF-kappaB subunit p65 and its DNA binding affinity.
  J Biol Chem, 281, 22409-22420.  
16336179 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.  
16154093 D.B.Huang, D.Vu, and G.Ghosh (2005).
NF-kappaB RelB forms an intertwined homodimer.
  Structure, 13, 1365-1373.
PDB codes: 1zk9 1zka
15879558 H.F.Luecke, and K.R.Yamamoto (2005).
The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression.
  Genes Dev, 19, 1116-1127.  
15102445 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, 21-27.  
15341737 Q.S.Xu, R.B.Kucera, R.J.Roberts, and H.C.Guo (2004).
An asymmetric complex of restriction endonuclease MspI on its palindromic DNA recognition site.
  Structure, 12, 1741-1747.
PDB code: 1sa3
14593105 Y.Yoshida, A.Kumar, Y.Koyama, H.Peng, A.Arman, J.A.Boch, and P.E.Auron (2004).
Interleukin 1 activates STAT3/nuclear factor-kappaB cross-talk via a unique TRAF6- and p65-dependent mechanism.
  J Biol Chem, 279, 1768-1776.  
14532125 A.Hoffmann, T.H.Leung, and D.Baltimore (2003).
Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities.
  EMBO J, 22, 5530-5539.  
12595558 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.  
12588973 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.  
12886018 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: 1ooa
12624092 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: 1hk6
12949493 M.J.Giffin, J.C.Stroud, D.L.Bates, K.D.von Koenig, J.Hardin, and L.Chen (2003).
Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.
  Nat Struct Biol, 10, 800-806.
PDB code: 1p7h
12947093 S.Hou, H.Guan, and R.P.Ricciardi (2003).
Phosphorylation of serine 337 of NF-kappaB p50 is critical for DNA binding.
  J Biol Chem, 278, 45994-45998.  
11967310 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.  
11970948 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: 1le5 1le9
11900552 B.Wellenzohn, W.Flader, R.H.Winger, A.Hallbrucker, E.Mayer, and K.R.Liedl (2002).
Indirect readout of the trp-repressor-operator complex by B-DNA's backbone conformation transitions.
  Biochemistry, 41, 4088-4095.  
12005436 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: 2i9t
11970949 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: 1lei
11780147 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: 1imh
12384592 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.  
11870918 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.  
11983155 S.Ghosh, and M.Karin (2002).
Missing pieces in the NF-kappaB puzzle.
  Cell, 109, S81-S96.  
12077338 S.Jia, R.D.Flores-Saaib, and A.J.Courey (2002).
The Dorsal Rel homology domain plays an active role in transcriptional regulation.
  Mol Cell Biol, 22, 5089-5099.  
12466564 X.Yang, S.E.Bassett, X.Li, B.A.Luxon, N.K.Herzog, R.E.Shope, J.Aronson, T.W.Prow, J.F.Leary, R.Kirby, A.D.Ellington, and D.G.Gorenstein (2002).
Construction and selection of bead-bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing.
  Nucleic Acids Res, 30, e132.  
11500489 A.J.García-Piñeres, V.Castro, G.Mora, T.J.Schmidt, E.Strunck, H.L.Pahl, and I.Merfort (2001).
Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones.
  J Biol Chem, 276, 39713-39720.  
11812834 B.Wellenzohn, W.Flader, R.H.Winger, A.Hallbrucker, E.Mayer, and K.R.Liedl (2001).
Exocyclic groups in the minor groove influence the backbone conformation of DNA.
  Nucleic Acids Res, 29, 5036-5043.  
11257229 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: 1hjb 1hjc 1io4
11572998 V.Haridas, C.J.Arntzen, and J.U.Gutterman (2001).
Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), inhibit activation of nuclear factor-kappaB by inhibiting both its nuclear localization and ability to bind DNA.
  Proc Natl Acad Sci U S A, 98, 11557-11562.  
10713070 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.  
10837071 M.Karin, and Y.Ben-Neriah (2000).
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
  Annu Rev Immunol, 18, 621-663.  
10801482 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.  
11228742 B.Kaltschmidt, T.Sparna, and C.Kaltschmidt (1999).
Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.
  Antioxid Redox Signal, 1, 129-144.  
10410794 C.Wolberger (1999).
Multiprotein-DNA complexes in transcriptional regulation.
  Annu Rev Biophys Biomol Struct, 28, 29-56.  
10425685 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: 1bvo
10368277 P.Cramer, and C.W.Müller (1999).
A firm hand on NFkappaB: structures of the IkappaBalpha-NFkappaB complex.
  Structure, 7, R1-R6.  
10592330 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, 231-243.  
10431175 S.G.Sedgwick, and S.J.Smerdon (1999).
The ankyrin repeat: a diversity of interactions on a common structural framework.
  Trends Biochem Sci, 24, 311-316.  
10426425 S.Natori, H.Shiraishi, S.Hori, and A.Kobayashi (1999).
The roles of Sarcophaga defense molecules in immunity and metamorphosis.
  Dev Comp Immunol, 23, 317-328.  
10612599 X.Yang, S.Fennewald, B.A.Luxon, J.Aronson, N.K.Herzog, and D.G.Gorenstein (1999).
Aptamers containing thymidine 3'-O-phosphorodithioates: synthesis and binding to nuclear factor-kappaB.
  Bioorg Med Chem Lett, 9, 3357-3362.  
9794820 C.Wolberger (1998).
Combinatorial transcription factors.
  Curr Opin Genet Dev, 8, 552-559.  
9837931 G.Lyss, A.Knorre, T.J.Schmidt, H.L.Pahl, and I.Merfort (1998).
The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65.
  J Biol Chem, 273, 33508-33516.  
  9566883 M.Latimer, M.K.Ernst, L.L.Dunn, M.Drutskaya, and N.R.Rice (1998).
The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers.
  Mol Cell Biol, 18, 2640-2649.  
9738011 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.  
9634693 T.K.Kerppola (1998).
Transcriptional cooperativity: bending over backwards and doing the flip.
  Structure, 6, 549-554.  
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.