1yvh
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(New page: 200px<br /> <applet load="1yvh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yvh, resolution 2.05Å" /> '''Crystal Structure o...)
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Revision as of 18:18, 12 November 2007
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Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide
Overview
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.
About this Structure
1YVH is a Protein complex structure of sequences from Homo sapiens with MG as ligand. 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
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