PDBsum entry 2k4d

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protein metals links
Ligase PDB id
Protein chain
83 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Ligase
Title: E2-c-cbl recognition is necessary but not sufficient for ubiquitination activity
Structure: E3 ubiquitin-protein ligase cbl. Chain: a. Fragment: ring domain, residues 358-437. Synonym: signal transduction protein cbl, proto-oncogenE C- cbl, casitas b-lineage lymphoma proto-oncogene, ring finger protein 55. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cbl, cbl2, rnf55. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: A.Huang,R.N.De Jong,H.Wienk,S.G.Winkler,H.T.M.Timmers, R.Boelens
Key ref:
A.Huang et al. (2009). E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity. J Mol Biol, 385, 507-519. PubMed id: 18996392 DOI: 10.1016/j.jmb.2008.10.044
06-Jun-08     Release date:   20-Jan-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P22681  (CBL_HUMAN) -  E3 ubiquitin-protein ligase CBL
906 a.a.
83 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of signaling   1 term 
  Biochemical function     ubiquitin-protein ligase activity     2 terms  


DOI no: 10.1016/j.jmb.2008.10.044 J Mol Biol 385:507-519 (2009)
PubMed id: 18996392  
E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity.
A.Huang, Jong, H.Wienk, G.S.Winkler, H.T.Timmers, R.Boelens.
The E2 ubiquitin-conjugating enzymes UbcH7 and UbcH5B both show specific binding to the RING (really interesting new gene) domain of the E3 ubiquitin-protein ligase c-Cbl, but UbcH7 hardly supports ubiquitination of c-Cbl and substrate in a reconstituted system. Here, we found that neither structural changes nor subtle differences in the E2-E3 interaction surface are possible explanations for the functional specificity of UbcH5B and UbcH7 in their interaction with c-Cbl. The quick transfer of ubiquitin from the UbcH5B-Ub thioester to c-Cbl or other ubiquitin acceptors suggests that UbcH5B might functionally be a relatively pliable E2 enzyme. In contrast, the UbcH7-Ub thioester is too stable to transfer ubiquitin under our assay conditions, indicating that UbcH7 might be a more specific E2 enzyme. Our results imply that the interaction specificity between c-Cbl and E2 is required but not sufficient for transfer of ubiquitin to potential targets.
  Selected figure(s)  
Figure 3.
Fig. 3. NMR solution structure of c-Cbl linker and RING domain (358–437). (a) Free NMR solution structure of c-Cbl linker and RING domain. (b) The solution structure of free c-Cbl RING finger domain (lime) superimposed on the crystal structure of the c-Cbl RING finger domain (gray) complexed to UbcH7 (PDB ID: 1FBV).
Figure 7.
Fig. 7. Comparison of surface properties of UbcH5B and UbcH7. (a) Top: electrostatic surface potential of UbcH5B was calculated using the APBS plugin to PyMOL and indicated as a charge scale from negative (red) to positive (blue). Bottom: surface representation of interaction sites on UbcH5B. The catalytic site (yellow), E2 vert, similar Ub binding interface (cyan), E3 binding interface (orange), and the noncovalent Ub-binding interface on UbcH5B (green) are indicated. (b) UbcH7 electrostatic surface potential (top) and interaction sites (bottom), colored as indicated under (a).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 385, 507-519) copyright 2009.  
  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.  
21151032 L.Bedford, J.Lowe, L.R.Dick, R.J.Mayer, and J.E.Brownell (2011).
Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets.
  Nat Rev Drug Discov, 10, 29-46.  
20681948 C.W.Liew, H.Sun, T.Hunter, and C.L.Day (2010).
RING domain dimerization is essential for RNF4 function.
  Biochem J, 431, 23-29.
PDB code: 3ng2
19489725 R.J.Deshaies, and C.A.Joazeiro (2009).
RING domain E3 ubiquitin ligases.
  Annu Rev Biochem, 78, 399-434.  
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