3bum

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[[Image:3bum.jpg|left|200px]]
[[Image:3bum.jpg|left|200px]]
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{{Structure
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|PDB= 3bum |SIZE=350|CAPTION= <scene name='initialview01'>3bum</scene>, resolution 2.000&Aring;
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The line below this paragraph, containing "STRUCTURE_3bum", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
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|GENE= SPRY2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CBL, CBL2, RNF55 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_3bum| PDB=3bum | SCENE= }}
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|RELATEDENTRY=[[3bun|3BUN]], [[3buo|3BUO]], [[3buw|3BUW]], [[3bux|3BUX]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bum OCA], [http://www.ebi.ac.uk/pdbsum/3bum PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bum RCSB]</span>
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'''Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2'''
'''Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2'''
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[[Category: Sivaraman, J.]]
[[Category: Sivaraman, J.]]
[[Category: Sun, Q.]]
[[Category: Sun, Q.]]
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[[Category: calcium]]
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[[Category: Calcium]]
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[[Category: complex]]
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[[Category: Complex]]
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[[Category: cytoplasm]]
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[[Category: Cytoplasm]]
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[[Category: developmental protein]]
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[[Category: Developmental protein]]
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[[Category: ligase]]
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[[Category: Ligase]]
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[[Category: Phosphoprotein]]
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[[Category: proto-oncogene]]
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[[Category: Proto-oncogene]]
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[[Category: sh2 domain]]
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[[Category: Sh2 domain]]
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[[Category: signal transduction]]
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[[Category: Signal transduction]]
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[[Category: ubl conjugation pathway]]
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[[Category: Ubl conjugation pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:07:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:29:09 2008''
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Revision as of 18:07, 4 May 2008

Template:STRUCTURE 3bum

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2


Overview

The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orientates the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.

About this Structure

3BUM is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates., Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J, EMBO J. 2008 Feb 14;. PMID:18273061 Page seeded by OCA on Sun May 4 21:07:17 2008

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