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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2007-8-6
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
474-85
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pubmed:meshHeading |
pubmed-meshheading:17679095-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17679095-Amino Acid Sequence,
pubmed-meshheading:17679095-Binding Sites,
pubmed-meshheading:17679095-Cell Line,
pubmed-meshheading:17679095-Crystallization,
pubmed-meshheading:17679095-Dimerization,
pubmed-meshheading:17679095-Enzyme Activation,
pubmed-meshheading:17679095-HeLa Cells,
pubmed-meshheading:17679095-Humans,
pubmed-meshheading:17679095-Immunoblotting,
pubmed-meshheading:17679095-Immunoprecipitation,
pubmed-meshheading:17679095-Kidney,
pubmed-meshheading:17679095-Molecular Sequence Data,
pubmed-meshheading:17679095-Mutagenesis, Site-Directed,
pubmed-meshheading:17679095-Protein Conformation,
pubmed-meshheading:17679095-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:17679095-Sequence Homology, Amino Acid,
pubmed-meshheading:17679095-Transfection,
pubmed-meshheading:17679095-Ubiquitin
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pubmed:year |
2007
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pubmed:articleTitle |
Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.
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pubmed:affiliation |
Department of Biochemistry, McGill University, Montréal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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