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| '''Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_15737992}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15737992 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15737992}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Phosphotyrosine]] | | [[Category: Phosphotyrosine]] |
| [[Category: X-ray crystallography]] | | [[Category: X-ray crystallography]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:50:26 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:20:09 2008'' |