View source for 1yvh

[[Image:1yvh.gif|left|200px]]

 {{Structure
|PDB= 1yvh |SIZE=350|CAPTION= <scene name='initialview01'>1yvh</scene>, resolution 2.05&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
|ACTIVITY= 
|GENE= CBL, CBL2, RNF55 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yvh OCA], [http://www.ebi.ac.uk/pdbsum/1yvh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yvh RCSB]</span>
}}

'''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 [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YVH 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:[http://www.ncbi.nlm.nih.gov/pubmed/15737992 15737992]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Hu, J.]]
[[Category: Hubbard, S R.]]
[[Category: adapter protein]]
[[Category: phosphotyrosine]]
[[Category: x-ray crystallography]]

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