PDBsum entry 2jz3

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protein Protein-protein interface(s) links
Transcription inhibitor/transcription PDB id
Protein chains
15 a.a. *
118 a.a. *
96 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription inhibitor/transcription
Title: Socs box elonginbc ternary complex
Structure: Suppressor of cytokine signaling 3. Chain: a. Fragment: socs box, unp residues 186-225. Synonym: socs-3, cytokine-inducible sh2 protein 3, cis-3, p 10. Engineered: yes. Transcription elongation factor b polypeptide 2. Chain: b. Synonym: elonginb, RNA polymerase ii transcription factor s
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
NMR struc: 20 models
Authors: J.J.Babon,J.Sabo,A.Soetopo,S.Yao,M.F.Bailey,J.Zhang,N.A.Nico R.S.Norton
Key ref:
J.J.Babon et al. (2008). The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase. J Mol Biol, 381, 928-940. PubMed id: 18590740 DOI: 10.1016/j.jmb.2008.06.038
27-Dec-07     Release date:   23-Sep-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O35718  (SOCS3_MOUSE) -  Suppressor of cytokine signaling 3
225 a.a.
15 a.a.
Protein chain
Pfam   ArchSchema ?
Q15370  (ELOB_HUMAN) -  Transcription elongation factor B polypeptide 2
118 a.a.
118 a.a.
Protein chain
Pfam   ArchSchema ?
P83940  (ELOC_MOUSE) -  Transcription elongation factor B polypeptide 1
112 a.a.
96 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular vesicular exosome   7 terms 
  Biological process     intracellular signal transduction   15 terms 
  Biochemical function     protein binding     2 terms  


DOI no: 10.1016/j.jmb.2008.06.038 J Mol Biol 381:928-940 (2008)
PubMed id: 18590740  
The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase.
J.J.Babon, J.K.Sabo, A.Soetopo, S.Yao, M.F.Bailey, J.G.Zhang, N.A.Nicola, R.S.Norton.
Suppressor of cytokine signalling 3 (SOCS3) is responsible for regulating the cellular response to a variety of cytokines, including interleukin 6 and leukaemia inhibitory factor. Identification of the SOCS box domain led to the hypothesis that SOCS3 can associate with functional E3 ubiquitin ligases and thereby induce the degradation of bound signalling proteins. This model relies upon an interaction between the SOCS box, elonginBC and a cullin protein that forms the E3 ligase scaffold. We have investigated this interaction in vitro using purified components and show that SOCS3 binds to elonginBC and cullin5 with high affinity. The SOCS3-elonginBC interaction was further characterised by determining the solution structure of the SOCS box-elonginBC ternary complex and by deletion and alanine scanning mutagenesis of the SOCS box. These studies revealed that conformational flexibility is a key feature of the SOCS-elonginBC interaction. In particular, the SOCS box is disordered in isolation and only becomes structured upon elonginBC association. The interaction depends upon the first 12 residues of the SOCS box domain and particularly on a deeply buried, conserved leucine. The SOCS box, when bound to elonginBC, binds tightly to cullin5 with 100 nM affinity. Domains upstream of the SOCS box are not required for elonginBC or cullin5 association, indicating that the SOCS box acts as an independent binding domain capable of recruiting elonginBC and cullin5 to promote E3 ligase formation.
  Selected figure(s)  
Figure 5.
Fig. 5. Tertiary structure of an SOCS3 SOCS box–elonginBC complex. (a) Ribbon diagram of the SOCS3 SOCS box (red) in complex with elonginC (blue) and elonginB (green). The interaction of the SOCS box occurs exclusively with elonginC and is mediated mostly by hydrophobic interactions. ElonginBC forms a tightly associated complex with the core of the association being a continuous β-sheet formed by residues from both proteins. A number of side-chain hydrophobic interactions further stabilise the complex. (b) Close view of the SOCS box elonginC interface with hydrophobic side chains from the SOCS box (red) labelled. The hydrophobic residues from elonginC (blue) that form the interface are shown in grey stick representation. (c) Ribbon diagram of the SOCS3 SOCS box in complex with elonginBC [same color scheme as in (a)] shown overlaid on the SOCS2/elonginBC structure (cyan).
Figure 6.
Fig. 6. Key residues required for elonginBC binding. An Ala scan of the SOCS3 SOCS box to determine residues required for elonginBC binding was performed. Co-expression of 12 SOCS box domain constructs, each containing a single Ala mutation, with elonginBC was performed in E. coli, and glutathione Sepharose was used to pull down GST-labelled proteins present in the cell lysate. (a) The following mutations completely interfered with elonginBC binding: Val1, Thr3, Leu4, Leu7, Cys8, Arg9 and Val12. Of these, only the L4A mutation completely abolished binding. (c) Residues identified by Ala scan are highlighted on a surface representation of elonginBC where hydrophobic residues on the surface of elonginC are shown in yellow. The BC box of SOCS3 (red) is shown in cartoon representation with important side chains displayed in “stick” representation. ElonginC is shown in blue and elonginB in green.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 381, 928-940) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21155715 A.Meenhuis, C.Verwijmeren, O.Roovers, and I.P.Touw (2011).
The deubiquitinating enzyme DUB2A enhances CSF3 signalling by attenuating lysosomal routing of the CSF3 receptor.
  Biochem J, 434, 343-351.  
21119685 L.Nie, Y.Zhao, W.Wu, Y.Z.Yang, H.C.Wang, and X.H.Sun (2011).
Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes.
  Cell Res, 21, 754-769.  
20532212 J.R.Bergeron, H.Huthoff, D.A.Veselkov, R.L.Beavil, P.J.Simpson, S.J.Matthews, M.H.Malim, and M.R.Sanderson (2010).
The SOCS-box of HIV-1 Vif interacts with ElonginBC by induced-folding to recruit its Cul5-containing ubiquitin ligase complex.
  PLoS Pathog, 6, e1000925.  
20463065 L.S.Wolfe, B.J.Stanley, C.Liu, W.K.Eliason, and Y.Xiong (2010).
Dissection of the HIV Vif interaction with human E3 ubiquitin ligase.
  J Virol, 84, 7135-7139.  
20047958 R.C.Edgar (2010).
Quality measures for protein alignment benchmarks.
  Nucleic Acids Res, 38, 2145-2153.  
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
19643666 B.J.Baker, L.N.Akhtar, and E.N.Benveniste (2009).
SOCS1 and SOCS3 in the control of CNS immunity.
  Trends Immunol, 30, 392-400.  
19385048 J.J.Babon, J.K.Sabo, J.G.Zhang, N.A.Nicola, and R.S.Norton (2009).
The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression.
  J Mol Biol, 387, 162-174.  
18948053 J.Piessevaux, D.Lavens, F.Peelman, and J.Tavernier (2008).
The many faces of the SOCS box.
  Cytokine Growth Factor Rev, 19, 371-381.  
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.