3buo

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{{STRUCTURE_3buo| PDB=3buo | SCENE= }}
{{STRUCTURE_3buo| PDB=3buo | SCENE= }}
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'''Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor''''
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===Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor'===
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 18273061 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18273061}}
==About this Structure==
==About this Structure==
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[[Category: Zinc]]
[[Category: Zinc]]
[[Category: Zinc-finger]]
[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:07:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:36:26 2008''

Revision as of 10:36, 27 July 2008

Image:3buo.png

Template:STRUCTURE 3buo

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in EGF receptor'

Template:ABSTRACT PUBMED 18273061

About this Structure

3BUO 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

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