2cbl: Difference between revisions
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'''N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70''' | '''N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70''' | ||
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[[Category: Meng, W.]] | [[Category: Meng, W.]] | ||
[[Category: Sawasdikosol, S.]] | [[Category: Sawasdikosol, S.]] | ||
[[Category: | [[Category: Phosphotyrosine binding]] | ||
[[Category: Proto-oncogene]] | |||
[[Category: | [[Category: Sh2]] | ||
[[Category: | [[Category: Signal transduction]] | ||
[[Category: | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:39:25 2008'' | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 21:39, 3 May 2008
N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70
OverviewOverview
Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium-binding domain, and a divergent SH2 domain that was not recognizable from the amino-acid sequence of the protein. The calcium-bound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module.
About this StructureAbout this Structure
2CBL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase., Meng W, Sawasdikosol S, Burakoff SJ, Eck MJ, Nature. 1999 Mar 4;398(6722):84-90. PMID:10078535 Page seeded by OCA on Sat May 3 21:39:25 2008