PDBsum entry 1mdm

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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
Protein chains
124 a.a. *
129 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Inhibited fragment of ets-1 and paired domain of pax5 bound to DNA
Structure: Pax5/ets binding site on the mb-1 promoter. Chain: c. Engineered: yes. Pax5/ets binding site on the mb-1 promoter. Chain: d. Engineered: yes. Paired box protein pax-5. Chain: a. Fragment: paired DNA-binding domain, residues 1-149.
Source: Synthetic: yes. Other_details: synthesised by the phosphoramidite method. Homo sapiens. Human. Organism_taxid: 9606. Gene: pax5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Mus musculus.
Biol. unit: Tetramer (from PQS)
2.80Å     R-factor:   0.259     R-free:   0.310
Authors: C.W.Garvie,M.A.Pufall,B.J.Graves,C.Wolberger
Key ref:
C.W.Garvie et al. (2002). Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships. J Biol Chem, 277, 45529-45536. PubMed id: 12221090 DOI: 10.1074/jbc.M206327200
07-Aug-02     Release date:   11-Dec-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q02548  (PAX5_HUMAN) -  Paired box protein Pax-5
391 a.a.
124 a.a.
Protein chain
Pfam   ArchSchema ?
P27577  (ETS1_MOUSE) -  Protein C-ets-1
440 a.a.
129 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     DNA binding     3 terms  


DOI no: 10.1074/jbc.M206327200 J Biol Chem 277:45529-45536 (2002)
PubMed id: 12221090  
Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships.
C.W.Garvie, M.A.Pufall, B.J.Graves, C.Wolberger.
The DNA-binding activity of the eukaryotic transcription factor Ets-1 (E26 avian erythroblastosis virus oncogene-E twenty-six) is negatively regulated by inhibitory regions that flank the ETS domain. Based on the results of solution studies, these N- and C-terminal inhibitory regions have been proposed to pack against the ETS domain and form an autoinhibitory module whose N terminus partially unfolds upon binding of Ets-1 to DNA. Mutations that disrupt autoinhibition of DNA binding also cause a structural change in the inhibitory region. We report here a crystallographic study of fragments of Ets-1 that provide structural details of the inhibitory module and the structural transition that accompanies DNA binding. The structures of free and DNA-bound Ets-1 fragments containing the ETS domain and the inhibitory regions confirm that the N-terminal inhibitory region contains two alpha-helices one of which unfolds upon Ets-1 binding to DNA. The observations from the crystal structure, coupled with mutagenesis experiments, allow us to propose a model for the inhibited form of Ets-1 and lend insight into the flexible interaction between Ets-1 and the acute myeloid leukemia 1 protein, AML1 (RUNX1).
  Selected figure(s)  
Figure 3.
Fig. 3. Crystal structure of Ets-1 N300. A, Ets-1 N300 molecule. The ETS domain is represented in magenta, whereas the inhibitory regions are represented in green. B, three-dimensional domain-swap dimer formed by one molecule of Ets-1 N300 (cyan) with the other Ets-1 N300 molecule (magenta) in the asymmetric unit. C, crystal packing contacts made by helix HI-1 from one Ets-1 N300 molecule (cyan) with the other Ets-1 N300 molecule (magenta) in the asymmetric unit. The residues involved in this interaction are labeled with a color denoting whether they come from the HI-1 helix of one Ets-1 N300 molecule (cyan) or from the hydrophobic pocket of the second Ets-1 N300 molecule (magenta).
Figure 6.
Fig. 6. Alternative states of Ets-1 N280. A, Ets-1 N280 undergoes a conformational change upon DNA binding. B, model of interaction between inhibitory domains of AML1, shown in red, and Ets-1 N280 on DNA. The helix HI-1 is modeled in a folded state, presumably stabilized by interactions with AML-1. Only the DNA binding domain of AML-1 is shown (35), however, additional N- and C-terminal regions, blocked in red, are necessary for cooperative interactions with Ets-1 (31).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 45529-45536) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20722567 D.Kumar, L.Luan, S.Pathak, D.Salhan, S.Magoon, and P.C.Singhal (2010).
Ang II enhances tubular cell Ets-1 expression and associated down stream signaling is mediated through AT1 receptors.
  Ren Fail, 32, 986-991.  
20079749 V.B.Agarkar, N.D.Babayeva, P.J.Wilder, A.Rizzino, and T.H.Tahirov (2010).
Crystal structure of mouse Elf3 C-terminal DNA-binding domain in complex with type II TGF-beta receptor promoter DNA.
  J Mol Biol, 397, 278-289.
PDB code: 3jtg
  20435626 V.Lulli, P.Romania, R.Riccioni, A.Boe, F.Lo-Coco, U.Testa, and G.Marziali (2010).
Transcriptional silencing of the ETS1 oncogene contributes to human granulocytic differentiation.
  Haematologica, 95, 1633-1641.  
19616560 D.Fitzsimmons, K.Lukin, R.Lutz, C.W.Garvie, C.Wolberger, and J.Hagman (2009).
Highly cooperative recruitment of Ets-1 and release of autoinhibition by Pax5.
  J Mol Biol, 392, 452-464.  
19465391 G.Leprivier, D.Baillat, A.Begue, B.Hartmann, and M.Aumercier (2009).
Ets-1 p51 and p42 isoforms differentially modulate Stromelysin-1 promoter according to induced DNA bend orientation.
  Nucleic Acids Res, 37, 4341-4352.  
19217849 H.Kamberaj, and A.van der Vaart (2009).
Correlated motions and interactions at the onset of the DNA-induced partial unfolding of Ets-1.
  Biophys J, 96, 1307-1317.  
19429892 N.A.Temiz, and C.J.Camacho (2009).
Experimentally based contact energies decode interactions responsible for protein-DNA affinity and the role of molecular waters at the binding interface.
  Nucleic Acids Res, 37, 4076-4088.  
18566588 E.P.Lamber, L.Vanhille, L.C.Textor, G.S.Kachalova, M.H.Sieweke, and M.Wilmanns (2008).
Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization.
  EMBO J, 27, 2006-2017.
PDB code: 2nny
18508761 Y.Liu, K.S.Matthews, and S.E.Bondos (2008).
Multiple intrinsically disordered sequences alter DNA binding by the homeodomain of the Drosophila hox protein ultrabithorax.
  J Biol Chem, 283, 20874-20887.  
  18323600 Y.Suwa, T.Nakamura, S.Toma, S.Ikemizu, H.Kai, and Y.Yamagata (2008).
Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA-binding domain of the Ets transcription factor in complex with target DNA.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 171-174.  
16138186 V.J.Dzau, and M.Lopez-Ilasaca (2005).
Searching for transcriptional regulators of Ang II-induced vascular pathology.
  J Clin Invest, 115, 2319-2322.  
12971829 J.Dittmer (2003).
The biology of the Ets1 proto-oncogene.
  Mol Cancer, 2, 29.  
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 code is shown on the right.