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1yvh

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{{STRUCTURE_1yvh| PDB=1yvh | SCENE= }}
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'''Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide'''
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===Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide===
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==Overview==
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The Cbl adapter proteins typically function to down-regulate activated protein tyrosine kinases and other signaling proteins by coupling them to the ubiquitination machinery for degradation by the proteasome. Cbl proteins bind to specific tyrosine-phosphorylated sequences in target proteins via the tyrosine kinase-binding (TKB) domain, which comprises a four-helix bundle, an EF-hand calcium-binding domain, and a non-conventional Src homology-2 domain. The previously derived consensus sequence for phosphotyrosine recognition by the Cbl TKB domain is NXpY(S/T)XXP (X denotes lesser residue preference), wherein specificity is conferred primarily by residues C-terminal to the phosphotyrosine. Cbl is recruited to and phosphorylated by the insulin receptor in adipose cells through the adapter protein APS. APS is phosphorylated by the insulin receptor on a C-terminal tyrosine residue, which then serves as a binding site for the Cbl TKB domain. Using x-ray crystallography, site-directed mutagenesis, and calorimetric studies, we have characterized the interaction between the Cbl TKB domain and the Cbl recruitment site in APS, which contains a sequence motif, RA(V/I)XNQpY(S/T), that is conserved in the related adapter proteins SH2-B and Lnk. These studies reveal a novel mode of phosphopeptide interaction with the Cbl TKB domain, in which N-terminal residues distal to the phosphotyrosine directly contact residues of the four-helix bundle of the TKB domain.
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(as it appears on PubMed at http://www.pubmed.gov), where 15737992 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15737992}}
==About this Structure==
==About this Structure==
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[[Category: Phosphotyrosine]]
[[Category: Phosphotyrosine]]
[[Category: X-ray crystallography]]
[[Category: X-ray crystallography]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:20:09 2008''

Revision as of 10:20, 27 July 2008

Template:STRUCTURE 1yvh

Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide

Template:ABSTRACT PUBMED 15737992

About this Structure

1YVH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins., Hu J, Hubbard SR, J Biol Chem. 2005 May 13;280(19):18943-9. Epub 2005 Feb 28. PMID:15737992

Page seeded by OCA on Sun Jul 27 13:20:09 2008

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