This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1yvh
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1yvh.gif|left|200px]] | [[Image:1yvh.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1yvh", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1yvh| PDB=1yvh | SCENE= }} | |
| - | | | + | |
| - | | | + | |
| - | }} | + | |
'''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''' | ||
| Line 27: | Line 24: | ||
[[Category: Hu, J.]] | [[Category: Hu, J.]] | ||
[[Category: Hubbard, S R.]] | [[Category: Hubbard, S R.]] | ||
| - | [[Category: | + | [[Category: Adapter protein]] |
| - | [[Category: | + | [[Category: Phosphotyrosine]] |
| - | [[Category: | + | [[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 | + | |
Revision as of 13:50, 3 May 2008
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. 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 Sat May 3 16:50:26 2008
