1b47
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1b47.gif|left|200px]] | [[Image:1b47.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1b47", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1b47| PDB=1b47 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''STRUCTURE OF THE N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE IN ZAP-70''' | '''STRUCTURE OF THE N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE IN ZAP-70''' | ||
| Line 29: | Line 26: | ||
[[Category: Meng, W.]] | [[Category: Meng, W.]] | ||
[[Category: Sawasdikosol, S.]] | [[Category: Sawasdikosol, S.]] | ||
| - | [[Category: | + | [[Category: Cbl]] |
| - | [[Category: | + | [[Category: Proto-oncogene]] |
| - | [[Category: | + | [[Category: Sh2]] |
| - | [[Category: | + | [[Category: Signal transduction]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:02:40 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:02, 2 May 2008
STRUCTURE OF THE N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE IN ZAP-70
Overview
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 Structure
1B47 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Fri May 2 11:02:40 2008
