PDBsum entry 1h89

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protein dna_rna metals Protein-protein interface(s) links
Transcription/DNA PDB id
Protein chains
64 a.a. *
115 a.a. *
__K ×2
Waters ×123
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Crystal structure of ternary protein-DNA complex2
Structure: Caat/enhancer binding protein beta. Chain: a, b. Fragment: residues 273-336. Synonym: c/ebp beta, nfil-6. Engineered: yes. Other_details: bzip domain. Myb proto-oncogene protein. Chain: c. Fragment: residues 35-193.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Mus musculus. House mouse. Organism_taxid: 10090. Synthetic: DNA fragment from chicken tom-1a promoter.
Biol. unit: Hetero-Pentamer (from PDB file)
2.45Å     R-factor:   0.229     R-free:   0.267
Authors: T.H.Tahirov,K.Ogata
Key ref:
T.H.Tahirov et al. (2002). Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter. Cell, 108, 57-70. PubMed id: 11792321 DOI: 10.1016/S0092-8674(01)00636-5
30-Jan-01     Release date:   28-Jan-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P17676  (CEBPB_HUMAN) -  CCAAT/enhancer-binding protein beta
345 a.a.
64 a.a.
Protein chain
Pfam   ArchSchema ?
P06876  (MYB_MOUSE) -  Transcriptional activator Myb
636 a.a.
115 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     chromatin binding     4 terms  


DOI no: 10.1016/S0092-8674(01)00636-5 Cell 108:57-70 (2002)
PubMed id: 11792321  
Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter.
T.H.Tahirov, K.Sato, E.Ichikawa-Iwata, M.Sasaki, T.Inoue-Bungo, M.Shiina, K.Kimura, S.Takata, A.Fujikawa, H.Morii, T.Kumasaka, M.Yamamoto, S.Ishii, K.Ogata.
c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBP beta to regulate transcription of myeloid-specific genes. To assess the structural basis for that difference, we determined the crystal structures of complexes comprised of the c-Myb or AMV v-Myb DNA-binding domain (DBD), the C/EBP beta DBD, and a promoter DNA fragment. Within the c-Myb complex, a DNA-bound C/EBP beta interacts with R2 of c-Myb bound to a different DNA fragment; point mutations in v-Myb R2 eliminate such interaction within the v-Myb complex. GST pull-down assays, luciferase trans-activation assays, and atomic force microscopy confirmed that the interaction of c-Myb and C/EBP beta observed in crystal mimics their long range interaction on the promoter, which is accompanied by intervening DNA looping.
  Selected figure(s)  
Figure 2.
Figure 2. DNA Recognition by c-Myb and AMV v-Myb(A and B) Schematic representations of DNA recognition by c-Myb (A) and AMV v-Myb (B). Dashed and solid lines depict intermolecular hydrogen bonds and van der Waals contacts, respectively. DNA bases labeled in red are involved in direct interactions with proteins.(C) Stereo view of specific interactions between c-Myb and DNA bases. The peptide backbone of c-Myb is drawn as a pink or blue tube in the R2 and R3 regions, respectively. Thin and bold dotted lines depict intermolecular hydrogen bonds and van der Waals interactions, respectively. Water molecules are shown as red balls.(D and E) Electrostatic surface potential of DNA-bound c-Myb R1R2R3 viewed from the front (D) and back (E); positively and negatively charged areas are colored blue and red, respectively.
Figure 3.
Figure 3. Structural Differences between c-Myb R2 and AMV v-Myb R2 and Close-Up Views of the Interactions among c-Myb, C/EBPβ, and DNA(A) Stereo view of the superimposed R2 domains within c-Myb (pink) and AMV v-Myb (gray) complexes. The peptide backbones are drawn as tubes, and the side chains of residues that are mutated or exhibit different conformations in AMV v-Myb are drawn as sticks.(B) A close-up view of the interactions between the Arg114 and Trp115 backbones and the DNA phosphate oxygens at G4′ within the c-Myb and AMV v-Myb complexes.(C) Stereo view of the c-Myb–C/EBPβ interaction site. Intermolecular hydrogen bonds and K^+-mediated interactions are represented by dotted lines. Parts of c-Myb and C/EBPβ chains A and B are drawn as pink, yellow, and green sticks, respectively. The part of the DNA backbone interacting with the C/EBPβ leucine zipper region is also shown. The metal binding sites of R1, R2, and R3 were confirmed by their high-resolution crystal structures (T.T. et al., submitted).(D) Summary of the intermolecular van der Waals interactions between c-Myb and C/EBPβ.(E) Stereo view of the c-Myb–C/EBPβ-DNA interaction site highlighting the interactions involved in stabilization of the α1–α2 loop of c-Myb R2. The peptide backbones of DNA-bound c-Myb (pink) and C/EBPβ chains A (yellow) and B (green) are drawn as tubes. Free c-Myb R2 (blue) is superimposed on the DNA-bound c-Myb R2. An alternative position for the disordered portion of the α1–α2 loop of the free c-Myb R2 is colored dark blue.
  The above figures are reprinted by permission from Cell Press: Cell (2002, 108, 57-70) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21525927 K.Yamada, T.D.Frouws, B.Angst, D.J.Fitzgerald, C.DeLuca, K.Schimmele, D.F.Sargent, and T.J.Richmond (2011).
Structure and mechanism of the chromatin remodelling factor ISW1a.
  Nature, 472, 448-453.
PDB codes: 2y9y 2y9z
22146299 T.Siggers, M.H.Duyzend, J.Reddy, S.Khan, and M.L.Bulyk (2011).
Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex.
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21376705 Y.Chen, J.Liu, H.Xu, Z.Luo, and C.Zhang (2011).
Overexpression of the c-Myb but not its leukemogenic mutant DNA-binding domain increased adipogenic differentiation in mesenchymal stem cells.
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20043041 L.Chen, S.Xu, X.Zeng, J.Li, W.Yin, Y.Chen, Z.Shao, and W.Jin (2010).
c-myb activates CXCL12 transcription in T47D and MCF7 breast cancer cells.
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20942926 L.M.Tran, D.R.Hyduke, and J.C.Liao (2010).
Trimming of mammalian transcriptional networks using network component analysis.
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19144704 C.M.McDonald, C.Petosa, and P.J.Farrell (2009).
Interaction of Epstein-Barr virus BZLF1 C-terminal tail structure and core zipper is required for DNA replication but not for promoter transactivation.
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19841477 C.Wilczek, O.Chayka, A.Plachetka, and K.H.Klempnauer (2009).
Myb-induced chromatin remodeling at a dual enhancer/promoter element involves non-coding rna transcription and is disrupted by oncogenic mutations of v-myb.
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19003992 C.Y.Yang, K.H.Chin, M.T.Yang, A.H.Wang, and S.H.Chou (2009).
Crystal structure of RecX: a potent regulatory protein of RecA from Xanthomonas campestris.
  Proteins, 74, 530-537.
PDB code: 3dfg
19519454 M.Miller (2009).
The importance of being flexible: the case of basic region leucine zipper transcriptional regulators.
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X-ray structure of the complex of regulatory subunits of human DNA polymerase delta.
  Cell Cycle, 7, 3026-3036.
PDB code: 3e0j
18840288 E.R.Ko, D.Ko, C.Chen, and J.S.Lipsick (2008).
A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding.
  Mol Cancer, 7, 77.  
18186486 J.Arunachalam, and N.Gautham (2008).
Hydrophobic clusters in protein structures.
  Proteins, 71, 2012-2025.  
18710950 K.R.Badri, Y.Zhou, U.Dhru, S.Aramgam, and L.Schuger (2008).
Effects of the SANT domain of tension-induced/inhibited proteins (TIPs), novel partners of the histone acetyltransferase p300, on p300 activity and TIP-6-induced adipogenesis.
  Mol Cell Biol, 28, 6358-6372.  
18004789 M.Kosloff, and R.Kolodny (2008).
Sequence-similar, structure-dissimilar protein pairs in the PDB.
  Proteins, 71, 891-902.  
18578568 S.C.Wolski, J.Kuper, P.Hänzelmann, J.J.Truglio, D.L.Croteau, B.Van Houten, and C.Kisker (2008).
Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD.
  PLoS Biol, 6, e149.
PDB code: 2vsf
18723894 T.Eydmann, E.Sommariva, T.Inagawa, S.Mian, A.J.Klar, and J.Z.Dalgaard (2008).
Rtf1-mediated eukaryotic site-specific replication termination.
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17214883 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.  
17599912 H.Wang, B.Larris, T.H.Peiris, L.Zhang, J.Le Lay, Y.Gao, and L.E.Greenbaum (2007).
C/EBPbeta activates E2F-regulated genes in vivo via recruitment of the coactivator CREB-binding protein/P300.
  J Biol Chem, 282, 24679-24688.  
17377988 J.R.Horton, S.J.Elgar, S.I.Khan, X.Zhang, P.A.Wade, and X.Cheng (2007).
Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI.
  Proteins, 67, 1198-1202.
PDB code: 2nog
17959653 O.Ivanova, D.Braas, and K.H.Klempnauer (2007).
Oncogenic point mutations in the Myb DNA-binding domain alter the DNA-binding properties of Myb at a physiological target gene.
  Nucleic Acids Res, 35, 7237-7247.  
17189474 R.G.Garces, W.Gillon, and E.F.Pai (2007).
Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties.
  Protein Sci, 16, 176-188.
PDB code: 2fv2
16885027 M.Yang, C.B.Gocke, X.Luo, D.Borek, D.R.Tomchick, M.Machius, Z.Otwinowski, and H.Yu (2006).
Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase.
  Mol Cell, 23, 377-387.
PDB code: 2iw5
16531230 N.Tochio, T.Umehara, S.Koshiba, M.Inoue, T.Yabuki, M.Aoki, E.Seki, S.Watanabe, Y.Tomo, M.Hanada, M.Ikari, M.Sato, T.Terada, T.Nagase, O.Ohara, M.Shirouzu, A.Tanaka, T.Kigawa, and S.Yokoyama (2006).
Solution structure of the SWIRM domain of human histone demethylase LSD1.
  Structure, 14, 457-468.
PDB code: 2com
16223730 J.A.Listman, N.Wara-aswapati, J.E.Race, L.W.Blystone, N.Walker-Kopp, Z.Yang, and P.E.Auron (2005).
Conserved ETS domain arginines mediate DNA binding, nuclear localization, and a novel mode of bZIP interaction.
  J Biol Chem, 280, 41421-41428.  
15641115 N.Morii, G.Kido, H.Suzuki, and H.Morii (2005).
Annular self-assembly of DNA molecular chains occurring in natural dry process of diluted solutions.
  Biopolymers, 77, 163-172.  
15601869 O.Chayka, J.Kintscher, D.Braas, and K.H.Klempnauer (2005).
v-Myb mediates cooperation of a cell-specific enhancer with the mim-1 promoter.
  Mol Cell Biol, 25, 499-511.  
15950878 S.Semsey, K.Virnik, and S.Adhya (2005).
A gamut of loops: meandering DNA.
  Trends Biochem Sci, 30, 334-341.  
15657951 X.C.Wei, J.Dohkan, H.Kishi, C.X.Wu, S.Kondo, and A.Muraguchi (2005).
Characterization of the proximal enhancer element and transcriptional regulatory factors for murine recombination activating gene-2.
  Eur J Immunol, 35, 612-621.  
16195416 X.Mo, E.Kowenz-Leutz, Y.Laumonnier, H.Xu, and A.Leutz (2005).
Histone H3 tail positioning and acetylation by the c-Myb but not the v-Myb DNA-binding SANT domain.
  Genes Dev, 19, 2447-2457.  
15308626 C.Kanei-Ishii, T.Nomura, J.Tanikawa, E.Ichikawa-Iwata, and S.Ishii (2004).
Differential sensitivity of v-Myb and c-Myb to Wnt-1-induced protein degradation.
  J Biol Chem, 279, 44582-44589.  
15237103 G.F.Heine, J.M.Hernandez, and E.Grotewold (2004).
Two cysteines in plant R2R3 MYB domains participate in REDOX-dependent DNA binding.
  J Biol Chem, 279, 37878-37885.  
15361138 I.M.Zimmermann, M.A.Heim, B.Weisshaar, and J.F.Uhrig (2004).
Comprehensive identification of Arabidopsis thaliana MYB transcription factors interacting with R/B-like BHLH proteins.
  Plant J, 40, 22-34.  
15509555 J.Tanikawa, T.Nomura, E.M.Macmillan, T.Shinagawa, W.Jin, K.Kokura, D.Baba, M.Shirakawa, T.J.Gonda, and S.Ishii (2004).
p53 suppresses c-Myb-induced trans-activation and transformation by recruiting the corepressor mSin3A.
  J Biol Chem, 279, 55393-55400.  
15527501 O.Nordgård, T...Andersen, and O.S.Gabrielsen (2004).
Selective inhibition of c-Myb DNA-binding by RNA polymers.
  BMC Biochem, 5, 15.  
14761981 T.Nomura, J.Tanikawa, H.Akimaru, C.Kanei-Ishii, E.Ichikawa-Iwata, M.M.Khan, H.Ito, and S.Ishii (2004).
Oncogenic activation of c-Myb correlates with a loss of negative regulation by TIF1beta and Ski.
  J Biol Chem, 279, 16715-16726.  
12574124 C.Schwartz, K.Beck, S.Mink, M.Schmolke, B.Budde, D.Wenning, and K.H.Klempnauer (2003).
Recruitment of p300 by C/EBPbeta triggers phosphorylation of p300 and modulates coactivator activity.
  EMBO J, 22, 882-892.  
12456674 K.B.Andersson, E.Kowenz-Leutz, E.M.Brendeford, A.H.Tygsett, A.Leutz, and O.S.Gabrielsen (2003).
Phosphorylation-dependent down-regulation of c-Myb DNA binding is abrogated by a point mutation in the v-myb oncogene.
  J Biol Chem, 278, 3816-3824.  
12581658 K.Ogata, K.Sato, T.H.Tahirov, and T.Tahirov (2003).
Eukaryotic transcriptional regulatory complexes: cooperativity from near and afar.
  Curr Opin Struct Biol, 13, 40-48.  
12578822 M.Miller, J.D.Shuman, T.Sebastian, Z.Dauter, and P.F.Johnson (2003).
Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha.
  J Biol Chem, 278, 15178-15184.
PDB code: 1nwq
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
12553908 S.K.Nair, and S.K.Burley (2003).
X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.
  Cell, 112, 193-205.
PDB codes: 1nkp 1nlw
12853487 S.Pathania, M.Jayaram, and R.M.Harshey (2003).
A unique right end-enhancer complex precedes synapsis of Mu ends: the enhancer is sequestered within the transpososome throughout transposition.
  EMBO J, 22, 3725-3736.  
14536084 T.Grüne, J.Brzeski, A.Eberharter, C.R.Clapier, D.F.Corona, P.B.Becker, and C.W.Müller (2003).
Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI.
  Mol Cell, 12, 449-460.
PDB code: 1ofc
12631292 ..Dahle, T...Andersen, O.Nordgård, V.Matre, G.Del Sal, and O.S.Gabrielsen (2003).
Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner.
  Eur J Biochem, 270, 1338-1348.  
12372296 A.Sidow (2002).
Sequence first. Ask questions later.
  Cell, 111, 13-16.  
12504020 P.Hatzis, and I.Talianidis (2002).
Dynamics of enhancer-promoter communication during differentiation-induced gene activation.
  Mol Cell, 10, 1467-1477.  
12086600 S.Pathania, M.Jayaram, and R.M.Harshey (2002).
Path of DNA within the Mu transpososome. Transposase interactions bridging two Mu ends and the enhancer trap five DNA supercoils.
  Cell, 109, 425-436.  
12032291 Y.Li, S.Mui, J.H.Brown, J.Strand, L.Reshetnikova, L.S.Tobacman, and C.Cohen (2002).
The crystal structure of the C-terminal fragment of striated-muscle alpha-tropomyosin reveals a key troponin T recognition site.
  Proc Natl Acad Sci U S A, 99, 7378-7383.
PDB code: 1kql
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