PDBsum entry 1wd2

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protein metals links
Ligase PDB id
Protein chain
60 a.a. *
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Solution structure of thE C-terminal ring from a ring-ibr- ring (triad) motif
Structure: Ariadne-1 protein homolog. Chain: a. Fragment: c-terminal ring. Synonym: ari-1, ubiquitin-conjugating enzyme e2- binding protein 1, ubch7-binding protein, ubcm4-interacting protein, hhari, h7-ap2, hussy-27, mop-6. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 20 models
Authors: A.D.Capili,E.L.Edghill,K.Wu,K.L.B.Borden
Key ref:
A.D.Capili et al. (2004). Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING. J Mol Biol, 340, 1117-1129. PubMed id: 15236971 DOI: 10.1016/j.jmb.2004.05.035
11-May-04     Release date:   20-Jul-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9Y4X5  (ARI1_HUMAN) -  E3 ubiquitin-protein ligase ARIH1
557 a.a.
60 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!
  Biochemical function     zinc ion binding     1 term  


DOI no: 10.1016/j.jmb.2004.05.035 J Mol Biol 340:1117-1129 (2004)
PubMed id: 15236971  
Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING.
A.D.Capili, E.L.Edghill, K.Wu, K.L.Borden.
The really interesting new gene (RING) family of proteins contains over 400 members with diverse physiological functions. A subset of these domains is found in the context of the RING-IBR-RING/TRIAD motifs which function as E3 ubiquitin ligases. Our sequence analysis of the C-terminal RING (RING2) from this motif show that several metal ligating and hydrophobic residues critical for the formation of a classical RING cross-brace structure are not present. Thus, we determined the structure of the RING2 from the RING-IBR-RING motif of HHARI and showed that RING2 has a completely distinct topology from classical RINGs. Notably, RING2 binds only one zinc atom per monomer rather than two and uses a different hydrophobic network to that of classical RINGs. Additionally, this RING2 topology is novel, bearing slight resemblance to zinc-ribbon motifs around the zinc site and is different from the topologies of the zinc binding sites found in RING and PHDs. We demonstrate that RING2 acts as an E3 ligase in vitro and using mutational analysis deduce the structural features required for this activity. Further, mutations in the RING-IBR-RING of Parkin cause a rare form of Parkinsonism and these studies provide an explanation for those mutations that occur in its RING2. From a comparison of the RING2 structure with those reported for RINGs, we infer sequence determinants that allow discrimination between RING2 and RING domains at the sequence analysis level.
  Selected figure(s)  
Figure 4.
Figure 4. The hydrophobic network used by RING2 differs from that of classical RING domains. (A) Sequence alignment with conserved hydrophobic residues in the RING2 family colored in green and conserved residues that form the hydrophobic core for classical RINGs in yellow. (B) View similar to Figure 3(B), depicting the positions of the conserved RING2 residues (green) and the residues that should form a hydrophobic core in classical RINGs (yellow). (C) View rotated about the y-axis by 90° and showing the Gly loop.
Figure 6.
Figure 6. RING2 has a distinct topology to a classical RING domain. Comparison of RING2 with the RING domain from Cbl (PDB code 1fbv). Images were rendered in PyMol and gray spheres represent zinc atoms.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 340, 1117-1129) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21532592 D.M.Wenzel, A.Lissounov, P.S.Brzovic, and R.E.Klevit (2011).
UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids.
  Nature, 474, 105-108.  
20585566 B.Wu, T.Skarina, A.Yee, M.C.Jobin, R.Dileo, A.Semesi, C.Fares, A.Lemak, B.K.Coombes, C.H.Arrowsmith, A.U.Singer, and A.Savchenko (2010).
NleG Type 3 effectors from enterohaemorrhagic Escherichia coli are U-Box E3 ubiquitin ligases.
  PLoS Pathog, 6, e1000960.
PDB codes: 2kkx 2kky
20126261 D.P.Narendra, S.M.Jin, A.Tanaka, D.F.Suen, C.A.Gautier, J.Shen, M.R.Cookson, and R.J.Youle (2010).
PINK1 is selectively stabilized on impaired mitochondria to activate Parkin.
  PLoS Biol, 8, e1000298.  
20644651 I.Marín (2010).
Diversification and Specialization of Plant RBR Ubiquitin Ligases.
  PLoS One, 5, e11579.  
19653100 E.C.Ambrose, and J.Kornbluth (2009).
Downregulation of uridine-cytidine kinase like-1 decreases proliferation and enhances tumor susceptibility to lysis by apoptotic agents and natural killer cells.
  Apoptosis, 14, 1227-1236.  
19526189 I.Marín (2009).
RBR ubiquitin ligases: Diversification and streamlining in animal lineages.
  J Mol Evol, 69, 54-64.  
19340006 J.A.Marteijn, L.T.van der Meer, J.J.Smit, S.M.Noordermeer, W.Wissink, P.Jansen, H.G.Swarts, R.G.Hibbert, Witte, T.K.Sixma, J.H.Jansen, and B.A.van der Reijden (2009).
The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains.
  Leukemia, 23, 1480-1489.  
19339245 V.A.Hristova, S.A.Beasley, R.J.Rylett, and G.S.Shaw (2009).
Identification of a Novel Zn2+-binding Domain in the Autosomal Recessive Juvenile Parkinson-related E3 Ligase Parkin.
  J Biol Chem, 284, 14978-14986.  
18362144 J.S.Schlehe, A.K.Lutz, A.Pilsl, K.Lämmermann, K.Grgur, I.H.Henn, J.Tatzelt, and K.F.Winklhofer (2008).
Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation.
  J Biol Chem, 283, 13771-13779.  
18655028 K.Miyamoto, H.Sakurai, and T.Sugiura (2008).
Proteomic identification of a PSF/p54nrb heterodimer as RNF43 oncoprotein-interacting proteins.
  Proteomics, 8, 2907-2910.  
17367545 B.Eisenhaber, N.Chumak, F.Eisenhaber, and M.T.Hauser (2007).
The ring between ring fingers (RBR) protein family.
  Genome Biol, 8, 209.  
17329252 E.S.Wong, J.M.Tan, C.Wang, Z.Zhang, S.P.Tay, N.Zaiden, H.S.Ko, V.L.Dawson, T.M.Dawson, and K.L.Lim (2007).
Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations.
  J Biol Chem, 282, 12310-12318.  
17976014 G.Koellensperger, S.Daubert, R.Erdmann, S.Hann, and H.Rottensteiner (2007).
Characterisation of zinc-binding domains of peroxisomal RING finger proteins using size exclusion chromatography/inductively coupled plasma-mass spectrometry.
  Biol Chem, 388, 1209-1214.  
17646546 J.A.Marteijn, L.T.van der Meer, L.van Emst, S.van Reijmersdal, W.Wissink, Witte, J.H.Jansen, and B.A.Van der Reijden (2007).
Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1.
  Blood, 110, 3128-3135.  
17360614 S.A.Beasley, V.A.Hristova, and G.S.Shaw (2007).
Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease.
  Proc Natl Acad Sci U S A, 104, 3095-3100.
PDB code: 2jmo
16641289 C.L.Afonso, E.R.Tulman, G.Delhon, Z.Lu, G.J.Viljoen, D.B.Wallace, G.F.Kutish, and D.L.Rock (2006).
Genome of crocodilepox virus.
  J Virol, 80, 4978-4991.  
16569227 V.Arnau, M.Gallach, J.I.Lucas, and I.Marín (2006).
UVPAR: fast detection of functional shifts in duplicate genes.
  BMC Bioinformatics, 7, 174.  
15601771 A.Kentsis, I.Topisirovic, B.Culjkovic, L.Shao, and K.L.Borden (2004).
Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap.
  Proc Natl Acad Sci U S A, 101, 18105-18110.  
15572841 R.Takahashi (2004).
[Neurodegeneration caused by ER stress?--the pathogenetic mechanisms underlying AR-JP]
  Nippon Yakurigaku Zasshi, 124, 375-382.  
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.