3VRP: Crystal Structure Of The Tyrosine Kinase Binding Domain Of Cbl-c In Complex With Phospho-egfr Peptide

Through their ubiquitin ligase activity, Cbl-family proteins suppress signalling mediated by protein-tyrosine kinases (PTKs), but can also function as adaptor proteins to positively regulate signalling. The tyrosine kinase binding (TKB) domain of this family is critical for binding with tyrosine-phosphorylated target proteins. Here, we analysed the crystal structure of the TKB domain of Cbl-c/Cbl-3 (Cbl-c TKB), which is a distinct member of the mammalian Cbl-family. In comparison with Cbl TKB, Cbl-c TKB showed restricted structural flexibility upon phosphopeptide binding. A mutation in Cbl-c TKB augmenting this flexibility enhanced its binding to target phosphoproteins. These results suggest that proteins, post-translational modifications or mutations that alter structural flexibility of the TKB domain of Cbl-family proteins could regulate their binding to target phosphoproteins and thereby, affect PTK-mediated signalling.
PDB ID: 3VRPDownload
MMDB ID: 108062
PDB Deposition Date: 2012/4/13
Updated in MMDB: 2013/03
Experimental Method:
x-ray diffraction
Resolution: 1.52  Å
Source Organism:
Similar Structures:
Biological Unit for 3VRP: dimeric; determined by author and by software (PISA)
Molecular Components in 3VRP
Label Count Molecule
Proteins (2 molecules)
Signal Transduction Protein Cbl-c(Gene symbol: CBLC)
Molecule annotation
Epidermal Growth Factor Receptor(Gene symbol: EGFR)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB