2OOA: Crystal Structure Of The Uba Domain From Cbl-B Ubiquitin Ligase

Cbl proteins are E3 ubiquitin ligases that are negative regulators of many receptor tyrosine kinases. Cbl-b and c-Cbl contain a ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Despite high sequence identity, Cbl UBA domains display remarkably different ubiquitin-binding properties. Here, we report the crystal structure of the UBA domain of Cbl-b in complex with ubiquitin at 1.9 A resolution. The structure reveals an atypical mechanism of ubiquitin recognition by the first helix of the UBA. Helices 2 and 3 of the UBA domain form a second binding surface, which mediates UBA dimerization in the crystal and in solution. Site-directed mutagenesis demonstrates that Cbl-b dimerization is regulated by ubiquitin binding and required for tyrosine phosphorylation of Cbl-b and ubiquitination of Cbl-b substrates. These studies demonstrate a role for ubiquitin in regulating biological activity by promoting protein dimerization.
PDB ID: 2OOADownload
MMDB ID: 44256
PDB Deposition Date: 2007/1/25
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.56  Å
Source Organism:
Similar Structures:
Biological Unit for 2OOA: monomeric; determined by author
Molecular Components in 2OOA
Label Count Molecule
Protein (1 molecule)
E3 Ubiquitin-protein Ligase Cbl-b(Gene symbol: CBLB)
Molecule annotation
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Citing MMDB