PDBsum entry 2h0d

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protein metals Protein-protein interface(s) links
Metal binding protein/ligase PDB id
Protein chains
97 a.a. *
100 a.a. *
_ZN ×4
Waters ×31
* Residue conservation analysis
PDB id:
Name: Metal binding protein/ligase
Title: Structure of a bmi-1-ring1b polycomb group ubiquitin ligase
Structure: B lymphoma mo-mlv insertion region. Chain: a. Fragment: residues 5-101. Engineered: yes. Ubiquitin ligase protein ring2. Chain: b. Fragment: residues 15-114. Synonym: ring finger protein 2, ring finger protein 1b, rin finger protein bap-1, ding protein, huntingtin-interacting
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.211     R-free:   0.244
Authors: R.M.Xu
Key ref:
Z.Li et al. (2006). Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem, 281, 20643-20649. PubMed id: 16714294 DOI: 10.1074/jbc.M602461200
14-May-06     Release date:   23-May-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P35226  (BMI1_HUMAN) -  Polycomb complex protein BMI-1
326 a.a.
97 a.a.
Protein chain
Pfam   ArchSchema ?
Q99496  (RING2_HUMAN) -  E3 ubiquitin-protein ligase RING2
336 a.a.
100 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     metal ion binding     2 terms  


DOI no: 10.1074/jbc.M602461200 J Biol Chem 281:20643-20649 (2006)
PubMed id: 16714294  
Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex.
Z.Li, R.Cao, M.Wang, M.P.Myers, Y.Zhang, R.M.Xu.
Polycomb group proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex, which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis, and stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5-A structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B "hugs" Bmi-1 through extensive RING domain contacts and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer.
  Selected figure(s)  
Figure 2.
FIGURE 2. Structure of the mini Bmi-1-Ring1B complex. A, a ribbon representation of the heterodimer structure. Bmi-1 and Ring1B are shown in cyan and orange, respectively. Zinc ions are shown as magenta spheres. Main secondary structure elements are labeled. B, a view of the heterodimer from the left side with respect to the view direction in A. C, the interface of Bmi-1 and Ring1B RING domains involves a mixture of hydrophobic and polar interactions. The residues involved are shown in a stick model (carbon: green for Bmi-1 and yellow for Ring1B; nitrogen: blue; oxygen: red; sulfur: orange) superimposed with the Ca chains (cyan, Bmi-1; orange, Ring1B). A salt bridge involving Asp-72 of Bmi-1 and Arg-70 of Ring1B is labeled. D, the N-terminal tail of Ring1B wraps around Bmi-1, which is shown in a surface representation and Ring1B in a stick model. The structure is viewed from a direction similar to that in B. The boxed area is shown in a close-in view in E. Thr-41 of Bmi-1 is buried in interactions with Glu-23 and Arg-26, and these residues are labeled.
Figure 4.
FIGURE 4. Structural comparison and modeling. A, superposition of the mini Bmi1-Ring1B complex with the BRCA1-BARD RING domain complex. The Ca chains of Bmi-1, Ring1B, BRCA1, and BARD are colored cyan, orange, green, and blue, respectively. The N and C termini of each chain are labeled with letters of the corresponding color. B, a surface representation of the mini Bmi-1-Ring1B complex with the surface of Ring1B colored yellow and Bmi-1 in white (left panel). The green surface patches indicate the positions occupied by residues that differ between Bmi-1 and Mel-18. The area enclosed in the red dotted ellipse indicates the implicated E2 enzyme binding site. C, the same protein surfaces viewed from the back with respect to the position in B. The area enclosed in the blue dotted ellipse is enriched with residues different between Bmi-1 and Mel-18, and the area may represent a substrate binding site. D, a schematic diagram showing a model for the E3 ligase function of the Bmi-1-Ring1B complex where the heterodimeric complex facilitates an efficient transfer by position the substrate and the E2 enzyme in an optimal configuration.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 20643-20649) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22902369 H.Dou, L.Buetow, G.J.Sibbet, K.Cameron, and D.T.Huang (2012).
BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer.
  Nat Struct Mol Biol, 19, 876-883.
PDB code: 4auq
21085188 R.L.Eckert, G.Adhikary, E.A.Rorke, Y.C.Chew, and S.Balasubramanian (2011).
Polycomb group proteins are key regulators of keratinocyte function.
  J Invest Dermatol, 131, 295-301.  
21294604 Y.W.Lin, H.M.Chen, and J.Y.Fang (2011).
Gene silencing by the Polycomb group proteins and associations with cancer.
  Cancer Invest, 29, 187-195.  
20569464 A.K.Yadav, A.A.Sahasrabuddhe, M.Dimri, P.V.Bommi, R.Sainger, and G.P.Dimri (2010).
Deletion analysis of BMI1 oncoprotein identifies its negative regulatory domain.
  Mol Cancer, 9, 158.  
20601937 G.N.Maertens, S.El Messaoudi-Aubert, S.Elderkin, K.Hiom, and G.Peters (2010).
Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor.
  EMBO J, 29, 2553-2565.  
20921134 I.H.Ismail, C.Andrin, D.McDonald, and M.J.Hendzel (2010).
BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair.
  J Cell Biol, 191, 45-60.  
20696397 R.Wang, A.B.Taylor, B.Z.Leal, L.V.Chadwell, U.Ilangovan, A.K.Robinson, V.Schirf, P.J.Hart, E.M.Lafer, B.Demeler, A.P.Hinck, D.G.McEwen, and C.A.Kim (2010).
Polycomb group targeting through different binding partners of RING1B C-terminal domain.
  Structure, 18, 966-975.
PDB codes: 3gs2 3ixs
20697353 T.Qian, J.Y.Lee, J.H.Park, H.J.Kim, and G.Kong (2010).
Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex.
  Oncogene, 29, 5818-5827.  
19886812 E.I.Campos, and D.Reinberg (2009).
Histones: annotating chromatin.
  Annu Rev Genet, 43, 559-599.  
19723311 H.E.Niessen, J.A.Demmers, and J.W.Voncken (2009).
Talking to chromatin: post-translational modulation of polycomb group function.
  Epigenetics Chromatin, 2, 10.  
19956605 I.Alchanati, C.Teicher, G.Cohen, V.Shemesh, H.M.Barr, P.Nakache, D.Ben-Avraham, A.Idelevich, I.Angel, N.Livnah, S.Tuvia, Y.Reiss, D.Taglicht, and O.Erez (2009).
The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target.
  PLoS One, 4, e8104.  
19738629 J.A.Simon, and R.E.Kingston (2009).
Mechanisms of polycomb gene silencing: knowns and unknowns.
  Nat Rev Mol Cell Biol, 10, 697-708.  
18781299 J.Bhattacharyya, K.Mihara, S.Yasunaga, H.Tanaka, M.Hoshi, Y.Takihara, and A.Kimura (2009).
BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia.
  Ann Hematol, 88, 333-340.  
19531475 J.Kim, and R.G.Roeder (2009).
Direct Bre1-Paf1 complex interactions and RING finger-independent Bre1-Rad6 interactions mediate histone H2B ubiquitylation in yeast.
  J Biol Chem, 284, 20582-20592.  
19345089 J.Müller, and P.Verrijzer (2009).
Biochemical mechanisms of gene regulation by polycomb group protein complexes.
  Curr Opin Genet Dev, 19, 150-158.  
19544461 M.Román-Trufero, H.R.Méndez-Gómez, C.Pérez, A.Hijikata, Y.Fujimura, T.Endo, H.Koseki, C.Vicario-Abejón, and M.Vidal (2009).
Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B.
  Stem Cells, 27, 1559-1570.  
19211678 O.Karakuzu, D.P.Wang, and S.Cameron (2009).
MIG-32 and SPAT-3A are PRC1 homologs that control neuronal migration in Caenorhabditis elegans.
  Development, 136, 943-953.  
19405034 P.S.Rao, A.Satelli, S.Zhang, S.K.Srivastava, K.S.Srivenugopal, and U.S.Rao (2009).
RNF2 is the target for phosphorylation by the p38 MAPK and ERK signaling pathways.
  Proteomics, 9, 2776-2787.  
19528329 R.B.Emmons, H.Genetti, S.Filandrinos, J.Lokere, and C.T.Wu (2009).
Molecular genetic analysis of Suppressor 2 of zeste identifies key functional domains.
  Genetics, 182, 999.  
19898523 R.S.Gieni, and M.J.Hendzel (2009).
Polycomb group protein gene silencing, non-coding RNA, stem cells, and cancer.
  Biochem Cell Biol, 87, 711-746.  
19889541 T.K.Kerppola (2009).
Polycomb group complexes--many combinations, many functions.
  Trends Cell Biol, 19, 692-704.  
18219319 K.Linke, P.D.Mace, C.A.Smith, D.L.Vaux, J.Silke, and C.L.Day (2008).
Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans.
  Cell Death Differ, 15, 841-848.
PDB codes: 2vje 2vjf
18588675 L.Sanchez-Pulido, D.Devos, Z.R.Sung, and M.Calonje (2008).
RAWUL: a new ubiquitin-like domain in PRC1 ring finger proteins that unveils putative plant and worm PRC1 orthologs.
  BMC Genomics, 9, 308.  
18086877 R.Cao, H.Wang, J.He, H.Erdjument-Bromage, P.Tempst, and Y.Zhang (2008).
Role of hPHF1 in H3K27 methylation and Hox gene silencing.
  Mol Cell Biol, 28, 1862-1872.  
18206973 X.Y.Zhang, M.Varthi, S.M.Sykes, C.Phillips, C.Warzecha, W.Zhu, A.Wyce, A.W.Thorne, S.L.Berger, and S.B.McMahon (2008).
The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression.
  Mol Cell, 29, 102-111.  
17477837 B.T.Dye, and B.A.Schulman (2007).
Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.
  Annu Rev Biophys Biomol Struct, 36, 131-150.  
17762864 H.Sun, J.D.Leverson, and T.Hunter (2007).
Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins.
  EMBO J, 26, 4102-4112.  
17179983 M.K.Kang, R.H.Kim, S.J.Kim, F.K.Yip, K.H.Shin, G.P.Dimri, R.Christensen, T.Han, and N.H.Park (2007).
Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival.
  Br J Cancer, 96, 126-133.  
17620408 M.Leeb, and A.Wutz (2007).
Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells.
  J Cell Biol, 178, 219-229.  
17933515 P.Knipscheer, and T.K.Sixma (2007).
Protein-protein interactions regulate Ubl conjugation.
  Curr Opin Struct Biol, 17, 665-673.  
17825942 S.J.Whitcomb, A.Basu, C.D.Allis, and E.Bernstein (2007).
Polycomb Group proteins: an evolutionary perspective.
  Trends Genet, 23, 494-502.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17173055 Y.B.Schwartz, and V.Pirrotta (2007).
Polycomb silencing mechanisms and the management of genomic programmes.
  Nat Rev Genet, 8, 9.  
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.