3bux

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models PDB ID 3bux Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.350Å
Ligands:
Gene:	CBL, CBL2, RNF55 (Homo sapiens)
Related:	3BUM, 3BUN, 3BUO, 3BUW
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in c-Met

Overview

The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orientates the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.

About this Structure

3BUX is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates., Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J, EMBO J. 2008 Feb 14;. PMID:18273061

Page seeded by OCA on Mon Mar 31 05:29:14 2008