3PLF

Reverse Binding Mode of MetRD peptide complexed with c-Cbl TKB domain

Summary for 3PLF

• Entry DOI: 10.2210/pdb3plf/pdb
• Descriptor: MetRD peptide, E3 ubiquitin-protein ligase CBL, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: c-cbl tkb domain, met, reverse binding, protein binding-ligase complex, protein binding/ligase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P22681
• Total number of polymer chains: 4
• Total formula weight: 79364.84

Authors

Sun, Q.,Sivaraman, J. (deposition date: 2010-11-15, release date: 2010-12-01, Last modification date: 2024-10-16)

Primary citation

Sun, Q.,Ng, C.,Guy, G.R.,Sivaraman, J.
An adjacent arginine, and the phosphorylated tyrosine in the c-Met receptor target sequence, dictates the orientation of c-Cbl binding
Febs Lett., 585:281-285, 2011

PubMed Abstract: 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.

PubMed: 21163258
DOI: 10.1016/j.febslet.2010.11.060

Experimental method

X-RAY DIFFRACTION (1.92 Å)