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2cbl
From Proteopedia
(New page: 200px<br /> <applet load="2cbl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cbl, resolution 2.1Å" /> '''N-TERMINAL DOMAIN OF...) |
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| - | [[Image:2cbl.gif|left|200px]]<br /> | + | [[Image:2cbl.gif|left|200px]]<br /><applet load="2cbl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2cbl" size=" | + | |
caption="2cbl, resolution 2.1Å" /> | caption="2cbl, resolution 2.1Å" /> | ||
'''N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70'''<br /> | '''N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cbl is an adaptor protein that functions as a negative regulator of many | + | 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== | ==About this Structure== | ||
| - | 2CBL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2CBL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CBL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Burakoff, S | + | [[Category: Burakoff, S J.]] |
| - | [[Category: Eck, M | + | [[Category: Eck, M J.]] |
[[Category: Meng, W.]] | [[Category: Meng, W.]] | ||
[[Category: Sawasdikosol, S.]] | [[Category: Sawasdikosol, S.]] | ||
| Line 25: | Line 24: | ||
[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:46:57 2008'' |
Revision as of 14:46, 21 February 2008
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N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON 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
2CBL is a Single protein structure of sequence from Homo sapiens with as ligand. 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
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