PDBsum entry 1k78

Go to PDB code: 
protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
Jmol PyMol
Protein chains
124 a.a. *
102 a.a. *
58 a.a. *
Waters ×484
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Pax5(1-149)+ets-1(331-440)+DNA
Structure: Pax5/ets binding site on the mb-1 promoter. Chain: c, g. Engineered: yes. Pax5/ets binding site on the mb-1 promoter. Chain: d, h. Engineered: yes. Paired box protein pax5. Chain: a, e, i. Fragment: paired domain.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: pax5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Mus musculus. House mouse.
Biol. unit: Tetramer (from PQS)
2.25Å     R-factor:   0.227     R-free:   0.260
Authors: C.W.Garvie,J.Hagman,C.Wolberger
Key ref:
C.W.Garvie et al. (2001). Structural studies of Ets-1/Pax5 complex formation on DNA. Mol Cell, 8, 1267-1276. PubMed id: 11779502 DOI: 10.1016/S1097-2765(01)00410-5
18-Oct-01     Release date:   04-Jan-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q02548  (PAX5_HUMAN) -  Paired box protein Pax-5
391 a.a.
124 a.a.
Protein chains
Pfam   ArchSchema ?
P27577  (ETS1_MOUSE) -  Protein C-ets-1
440 a.a.
102 a.a.
Protein chain
Pfam   ArchSchema ?
Q02548  (PAX5_HUMAN) -  Paired box protein Pax-5
391 a.a.
58 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: 10.1016/S1097-2765(01)00410-5 Mol Cell 8:1267-1276 (2001)
PubMed id: 11779502  
Structural studies of Ets-1/Pax5 complex formation on DNA.
C.W.Garvie, J.Hagman, C.Wolberger.
Pax5 regulates the B cell-specific expression of the mb-1 gene together with members of the Ets family of transcriptional activators. The Ets proteins on their own bind poorly to the Pax5/Ets binding site, but can be recruited to the site by cooperative interactions with Pax5. The structure of the ETS domain of Ets-1 and the paired domain of Pax5 bound to DNA reveals the molecular details of the selective recruitment of different Ets proteins by Pax5. Comparison with structures of Ets-1 alone bound to both high- and low-affinity DNA sites reveals that Pax5 alters the Ets-1 contacts with DNA. The ability of one protein to alter the DNA sequence-specific contacts of another provides a general mechanism for combinatorial regulation of transcription.
  Selected figure(s)  
Figure 3.
Figure 3. Residues Involved in the Interface between Pax5 and Ets-1 and Comparison with the Related Residues from Other Ets Proteins(A) Interface between Pax5 and Ets-1. The residues involved in the interface are labeled with a color denoting whether they came from the ETS domain (purple) or paired domain (blue). Hydrogen bonds and van der Waals contacts are indicated with dashed yellow lines. The DNA contacts made by Tyr395 are not shown in this depiction.(B) Sequence alignment of the ETS domains of Ets-1, Fli-1, GABPα, Net-1, Elk-1 and SAP-1. The secondary structure elements and the residue numbers of the ETS domain of Ets-1 are indicated above the protein sequence. α helices are depicted by rectangles and β strands as arrows. ETS domain residues with the same sequence as Ets-1 are highlighted in yellow. The Ets-1 residues involved in the Pax5/Ets-1 interface are indicated above the protein sequence.
Figure 5.
Figure 5. Conformational Switch of Tyr395 Of Ets-1 Induced by the Presence of Pax5
  The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 1267-1276) copyright 2001.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20943750 S.H.Cross, L.McKie, K.West, E.L.Coghill, J.Favor, S.Bhattacharya, S.D.Brown, and I.J.Jackson (2011).
The Opdc missense mutation of Pax2 has a milder than loss-of-function phenotype.
  Hum Mol Genet, 20, 223-234.  
20517297 G.H.Wei, G.Badis, M.F.Berger, T.Kivioja, K.Palin, M.Enge, M.Bonke, A.Jolma, M.Varjosalo, A.R.Gehrke, J.Yan, S.Talukder, M.Turunen, M.Taipale, H.G.Stunnenberg, E.Ukkonen, T.R.Hughes, M.L.Bulyk, and J.Taipale (2010).
Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo.
  EMBO J, 29, 2147-2160.  
20174675 J.Simicevic, and B.Deplancke (2010).
DNA-centered approaches to characterize regulatory protein-DNA interaction complexes.
  Mol Biosyst, 6, 462-468.  
  20827386 K.Gangwal, D.Close, C.A.Enriquez, C.P.Hill, and S.L.Lessnick (2010).
Emergent Properties of EWS/FLI Regulation via GGAA Microsatellites in Ewing's Sarcoma.
  Genes Cancer, 1, 177-187.  
20454645 P.Oettgen (2010).
The role of ets factors in tumor angiogenesis.
  J Oncol, 2010, 767384.  
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
20169177 W.Yang, N.Shen, D.Q.Ye, Q.Liu, Y.Zhang, X.X.Qian, N.Hirankarn, D.Ying, H.F.Pan, C.C.Mok, T.M.Chan, R.W.Wong, K.W.Lee, M.Y.Mok, S.N.Wong, A.M.Leung, X.P.Li, Y.Avihingsanon, C.M.Wong, T.L.Lee, M.H.Ho, P.P.Lee, Y.K.Chang, P.H.Li, R.J.Li, L.Zhang, W.H.Wong, I.O.Ng, C.S.Lau, P.C.Sham, Y.L.Lau, Y.L.Lau, N.Shen, D.Q.Ye, N.Hirankarn, and W.Yang (2010).
Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus.
  PLoS Genet, 6, e1000841.  
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.  
19336585 H.C.Yang, L.Shen, R.F.Siliciano, and J.L.Pomerantz (2009).
Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation.
  Proc Natl Acad Sci U S A, 106, 6321-6326.  
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.  
19429910 Y.Wang, J.C.Groppe, J.Wu, T.Ogawa, G.Mues, R.N.D'Souza, and H.Kapadia (2009).
Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.
  Hum Mol Genet, 18, 2863-2874.  
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
18552207 K.Walter, C.Bonifer, and H.Tagoh (2008).
Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus.
  Blood, 112, 1673-1682.  
18829450 L.Codutti, H.van Ingen, C.Vascotto, F.Fogolari, A.Corazza, G.Tell, F.Quadrifoglio, P.Viglino, R.Boelens, and G.Esposito (2008).
The Solution Structure of DNA-free Pax-8 Paired Box Domain Accounts for Redox Regulation of Transcriptional Activity in the Pax Protein Family.
  J Biol Chem, 283, 33321-33328.
PDB code: 2k27
17998914 M.L.Holmes, C.Pridans, and S.L.Nutt (2008).
The regulation of the B-cell gene expression programme by Pax5.
  Immunol Cell Biol, 86, 47-53.  
18478582 P.Poulain, A.Saladin, B.Hartmann, and C.Prévost (2008).
Insights on protein-DNA recognition by coarse grain modelling.
  J Comput Chem, 29, 2582-2592.  
18606452 S.Fields, K.Ternyak, H.Gao, R.Ostraat, J.Akerlund, and J.Hagman (2008).
The 'zinc knuckle' motif of Early B cell Factor is required for transcriptional activation of B cell-specific genes.
  Mol Immunol, 45, 3786-3796.  
  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.  
17440452 C.Cobaleda, A.Schebesta, A.Delogu, and M.Busslinger (2007).
Pax5: the guardian of B cell identity and function.
  Nat Immunol, 8, 463-470.  
17344859 C.G.Mullighan, S.Goorha, I.Radtke, C.B.Miller, E.Coustan-Smith, J.D.Dalton, K.Girtman, S.Mathew, J.Ma, S.B.Pounds, X.Su, C.H.Pui, M.V.Relling, W.E.Evans, S.A.Shurtleff, and J.R.Downing (2007).
Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.
  Nature, 446, 758-764.  
17148437 J.L.Kopp, P.J.Wilder, M.Desler, L.Kinarsky, and A.Rizzino (2007).
Different domains of the transcription factor ELF3 are required in a promoter-specific manner and multiple domains control its binding to DNA.
  J Biol Chem, 282, 3027-3041.  
17101802 S.Roessler, I.Györy, S.Imhof, M.Spivakov, R.R.Williams, M.Busslinger, A.G.Fisher, and R.Grosschedl (2007).
Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5.
  Mol Cell Biol, 27, 579-594.  
16482219 H.Tagoh, R.Ingram, N.Wilson, G.Salvagiotto, A.J.Warren, D.Clarke, M.Busslinger, and C.Bonifer (2006).
The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction.
  EMBO J, 25, 1070-1080.  
16537893 S.Kim, C.T.Denny, and R.Wisdom (2006).
Cooperative DNA binding with AP-1 proteins is required for transformation by EWS-Ets fusion proteins.
  Mol Cell Biol, 26, 2467-2478.  
16352813 X.Huang, C.Brown, W.Ni, E.Maynard, A.C.Rigby, and P.Oettgen (2006).
Critical role for the Ets transcription factor ELF-1 in the development of tumor angiogenesis.
  Blood, 107, 3153-3160.  
16680144 Z.Zhang, C.R.Espinoza, Z.Yu, R.Stephan, T.He, G.S.Williams, P.D.Burrows, J.Hagman, A.J.Feeney, and M.D.Cooper (2006).
Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.
  Nat Immunol, 7, 616-624.  
15591056 G.M.Lee, L.W.Donaldson, M.A.Pufall, H.S.Kang, I.Pot, B.J.Graves, and L.P.McIntosh (2005).
The structural and dynamic basis of Ets-1 DNA binding autoinhibition.
  J Biol Chem, 280, 7088-7099.
PDB code: 1r36
15994560 M.A.Pufall, G.M.Lee, M.L.Nelson, H.S.Kang, A.Velyvis, L.E.Kay, L.P.McIntosh, and B.J.Graves (2005).
Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region.
  Science, 309, 142-145.  
15558475 A.Cvekl, Y.Yang, B.K.Chauhan, and K.Cveklova (2004).
Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens.
  Int J Dev Biol, 48, 829-844.  
15123671 H.Liu, M.Holm, X.Q.Xie, M.Wolf-Watz, and T.Grundström (2004).
AML1/Runx1 recruits calcineurin to regulate granulocyte macrophage colony-stimulating factor by Ets1 activation.
  J Biol Chem, 279, 29398-29408.  
14976186 J.L.Kopp, P.J.Wilder, M.Desler, J.H.Kim, J.Hou, T.Nowling, and A.Rizzino (2004).
Unique and selective effects of five Ets family members, Elf3, Ets1, Ets2, PEA3, and PU.1, on the promoter of the type II transforming growth factor-beta receptor gene.
  J Biol Chem, 279, 19407-19420.  
14673175 J.Lu, M.J.Pazin, and K.Ravid (2004).
Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression.
  Mol Cell Biol, 24, 428-441.  
15032574 M.Busslinger (2004).
Transcriptional control of early B cell development.
  Annu Rev Immunol, 22, 55-79.  
14570912 S.Ano, R.Pereira, M.Pironin, I.Lesault, C.Milley, I.Lebigot, C.T.Quang, and J.Ghysdael (2004).
Erythroblast transformation by FLI-1 depends upon its specific DNA binding and transcriptional activation properties.
  J Biol Chem, 279, 2993-3002.  
15304566 S.Watkins, G.van Pouderoyen, and T.K.Sixma (2004).
Structural analysis of the bipartite DNA-binding domain of Tc3 transposase bound to transposon DNA.
  Nucleic Acids Res, 32, 4306-4312.
PDB code: 1u78
12538894 A.Ke, and C.Wolberger (2003).
Insights into binding cooperativity of MATa1/MATalpha2 from the crystal structure of a MATa1 homeodomain-maltose binding protein chimera.
  Protein Sci, 12, 306-312.
PDB codes: 1mh3 1mh4
12612069 H.Maier, J.Colbert, D.Fitzsimmons, D.R.Clark, and J.Hagman (2003).
Activation of the early B-cell-specific mb-1 (Ig-alpha) gene by Pax-5 is dependent on an unmethylated Ets binding site.
  Mol Cell Biol, 23, 1946-1960.  
14500810 H.Maier, R.Ostraat, S.Parenti, D.Fitzsimmons, L.J.Abraham, C.W.Garvie, and J.Hagman (2003).
Requirements for selective recruitment of Ets proteins and activation of mb-1/Ig-alpha gene transcription by Pax-5 (BSAP).
  Nucleic Acids Res, 31, 5483-5489.  
12971829 J.Dittmer (2003).
The biology of the Ets1 proto-oncogene.
  Mol Cancer, 2, 29.  
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.  
12633666 L.A.Warren, E.V.Rothenberg, and E.V.Rothenberg (2003).
Regulatory coding of lymphoid lineage choice by hematopoietic transcription factors.
  Curr Opin Immunol, 15, 166-175.  
14673097 S.Y.Reddy, S.Obika, and T.C.Bruice (2003).
Conformations and dynamics of Ets-1 ETS domain-DNA complexes.
  Proc Natl Acad Sci U S A, 100, 15475-15480.  
11839497 A.J.Warren (2002).
Eukaryotic transcription factors.
  Curr Opin Struct Biol, 12, 107-114.  
12453417 C.R.Escalante, A.L.Brass, J.M.Pongubala, E.Shatova, L.Shen, H.Singh, and A.K.Aggarwal (2002).
Crystal structure of PU.1/IRF-4/DNA ternary complex.
  Mol Cell, 10, 1097-1105.  
12221090 C.W.Garvie, M.A.Pufall, B.J.Graves, and C.Wolberger (2002).
Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships.
  J Biol Chem, 277, 45529-45536.
PDB codes: 1md0 1mdm
12034715 D.Baillat, A.Bègue, D.Stéhelin, and M.Aumercier (2002).
ETS-1 transcription factor binds cooperatively to the palindromic head to head ETS-binding sites of the stromelysin-1 promoter by counteracting autoinhibition.
  J Biol Chem, 277, 29386-29398.  
12457614 H.Maier, and J.Hagman (2002).
Roles of EBF and Pax-5 in B lineage commitment and development.
  Semin Immunol, 14, 415-422.  
12087183 L.De Haro, and R.Janknecht (2002).
Functional analysis of the transcription factor ER71 and its activation of the matrix metalloproteinase-1 promoter.
  Nucleic Acids Res, 30, 2972-2979.  
12142282 M.A.Pufall, and B.J.Graves (2002).
Autoinhibitory domains: modular effectors of cellular regulation.
  Annu Rev Cell Dev Biol, 18, 421-462.  
12446773 M.Sigvardsson, D.R.Clark, D.Fitzsimmons, M.Doyle, P.Akerblad, T.Breslin, S.Bilke, R.Li, C.Yeamans, G.Zhang, and J.Hagman (2002).
Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter.
  Mol Cell Biol, 22, 8539-8551.  
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.