2OOA

crystal structure of the UBA domain from Cbl-b ubiquitin ligase

Summary for 2OOA

• Entry DOI: 10.2210/pdb2ooa/pdb
• Related: 2OO9 2OOB
• Descriptor: E3 ubiquitin-protein ligase CBL-B (2 entities in total)
• Functional Keywords: alpha-helical domain, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q13191
• Total number of polymer chains: 2
• Total formula weight: 11406.55

Authors

Kozlov, G.,Gehring, K. (deposition date: 2007-01-25, release date: 2007-02-06, Last modification date: 2024-11-13)

Primary citation

Peschard, P.,Kozlov, G.,Lin, T.,Mirza, I.A.,Berghuis, A.M.,Lipkowitz, S.,Park, M.,Gehring, K.
Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.
Mol.Cell, 27:474-485, 2007

PubMed Abstract: 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.

PubMed: 17679095
DOI: 10.1016/j.molcel.2007.06.023

Experimental method

X-RAY DIFFRACTION (1.56 Å)