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PDBsum entry 3pse

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protein ligands Protein-protein interface(s) links
Hydrolase/protein binding PDB id
3pse
Jmol
Contents
Protein chains
164 a.a. *
150 a.a. *
Ligands
3CN
GOL
Waters ×139
* Residue conservation analysis
PDB id:
3pse
Name: Hydrolase/protein binding
Title: Structure of a viral otu domain protease bound to interferon stimulated gene 15 (isg15)
Structure: RNA polymerase. Chain: a. Fragment: otu domain (unp residues 1-169). Engineered: yes. Ubiquitin-like protein isg15. Chain: b. Synonym: interferon-induced 15 kda protein, interferon-indu protein, ip17, ubiquitin cross-reactive protein, hucrp. Engineered: yes.
Source: Crimean-congo hemorrhagic fever virus. Organism_taxid: 11593. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: isg15, g1p2, ucrp. Expression_system_taxid: 562
Resolution:
2.30Å     R-factor:   0.167     R-free:   0.224
Authors: J.P.Bacik,T.W.James,N.Frias-Staheli,A.Garcia-Sastre,B.L.Mark
Key ref: T.W.James et al. (2011). Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease. Proc Natl Acad Sci U S A, 108, 2222-2227. PubMed id: 21245344
Date:
01-Dec-10     Release date:   19-Jan-11    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q6TQF5  (Q6TQF5_9VIRU) -  Putative RNA polymerase
Seq:
Struc:
 
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Seq:
Struc:
3945 a.a.
164 a.a.
Protein chain
Pfam   ArchSchema ?
P05161  (ISG15_HUMAN) -  Ubiquitin-like protein ISG15
Seq:
Struc:
165 a.a.
150 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     immune system process   15 terms 
  Biochemical function     protein tag     2 terms  

 

 
Proc Natl Acad Sci U S A 108:2222-2227 (2011)
PubMed id: 21245344  
 
 
Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease.
T.W.James, N.Frias-Staheli, J.P.Bacik, J.M.Levingston Macleod, M.Khajehpour, A.García-Sastre, B.L.Mark.
 
  ABSTRACT  
 
The attachment of ubiquitin (Ub) and the Ub-like (Ubl) molecule interferon-stimulated gene 15 (ISG15) to cellular proteins mediates important innate antiviral responses. Ovarian tumor (OTU) domain proteases from nairoviruses and arteriviruses were recently found to remove these molecules from host proteins, which inhibits Ub and ISG15-dependent antiviral pathways. This contrasts with the Ub-specific activity of known eukaryotic OTU-domain proteases. Here we describe crystal structures of a viral OTU domain from the highly pathogenic Crimean-Congo haemorrhagic fever virus (CCHFV) bound to Ub and to ISG15 at 2.5-Å and 2.3-Å resolution, respectively. The complexes provide a unique structural example of ISG15 bound to another protein and reveal the molecular mechanism of an ISG15 cross-reactive deubiquitinase. To accommodate structural differences between Ub and ISG15, the viral protease binds the β-grasp folds of Ub and C-terminal Ub-like domain of ISG15 in an orientation that is rotated nearly 75° with respect to that observed for Ub bound to a representative eukaryotic OTU domain from yeast. Distinct structural determinants necessary for binding either substrate were identified and allowed the reengineering of the viral OTU protease into enzymes with increased substrate specificity, either for Ub or for ISG15. Our findings now provide the basis to determine in vivo the relative contributions of deubiquitination and deISGylation to viral immune evasion tactics, and a structural template of a promiscuous deubiquitinase from a haemorrhagic fever virus that can be targeted for inhibition using small-molecule-based strategies.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22157957 J.D.Licchesi, J.Mieszczanek, T.E.Mevissen, T.J.Rutherford, M.Akutsu, S.Virdee, F.El Oualid, J.W.Chin, H.Ovaa, M.Bienz, and D.Komander (2012).
An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains.
  Nat Struct Mol Biol, 19, 62-71.
PDB code: 3zrh
22367539 R.Wiener, X.Zhang, T.Wang, and C.Wolberger (2012).
The mechanism of OTUB1-mediated inhibition of ubiquitination.
  Nature, 483, 618-622.
PDB codes: 4dhi 4dhj 4dhz
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.