An adjacent arginine, and the phosphorylated tyrosine in the c-Met receptor target sequence, dictates the orientation of c-Cbl binding.

Previously, we have demonstrated that the tyrosine phosphorylated hepatocyte growth factor receptor (Met) binds to the c-Cbl phosphotyrosine-recognition, tyrosine kinase binding (TKB) domain in a reverse orientation compared to other c-Cbl binding partners. A Met peptide with the DpYR motif changed to RpYD (MetRD) retains a similar TKB binding affinity ...
as the native Met peptide. However, the TKB: MetRD complex crystal structure reveals a complete reversal of the binding orientation. Collated data indicates that both binding and orientation is dictated by the phosphorylated tyrosine and an adjacent arginine forming intra-peptide hydrogen bonds and aligning unidirectionally with complementary charges in the phosphotyrosine binding pocket of c-Cbl.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Arginine, Crystallography, X-Ray, Humans, Hydrogen Bonding, Kinetics, Mass Spectrometry, Phosphotyrosine, Protein Binding, Proto-Oncogene Proteins c-cbl, Proto-Oncogene Proteins c-met, Receptors, Growth Factor, Surface Plasmon Resonance
FEBS Lett.
Date: Jan. 21, 2011
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