1yvh
From Proteopedia
(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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| - | [[Image:1yvh.gif|left|200px]]<br /> | + | [[Image:1yvh.gif|left|200px]]<br /><applet load="1yvh" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1yvh, resolution 2.05Å" /> | caption="1yvh, resolution 2.05Å" /> | ||
'''Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide'''<br /> | '''Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Cbl adapter proteins typically function to down-regulate activated | + | 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== | ==About this Structure== | ||
| - | 1YVH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YVH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YVH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Hu, J.]] | [[Category: Hu, J.]] | ||
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: x-ray crystallography; phosphotyrosine; adapter protein]] | [[Category: x-ray crystallography; phosphotyrosine; adapter protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:09:32 2008'' |
Revision as of 14:09, 21 February 2008
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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 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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