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| {{STRUCTURE_3bum| PDB=3bum | SCENE= }} | | {{STRUCTURE_3bum| PDB=3bum | SCENE= }} |
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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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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_18273061}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18273061 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18273061}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Zinc]] | | [[Category: Zinc]] |
| [[Category: Zinc-finger]] | | [[Category: Zinc-finger]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:07:17 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:49:42 2008'' |
