3bux | pdb_00003bux
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| 3bux, resolution 1.350Å | |||||||||||||
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| Ligands: | PTR | ||||||||||||
| Gene: | CBL, CBL2, RNF55 (Homo sapiens) | ||||||||||||
| Related: | 3BUM, 3BUN, 3BUO, 3BUW
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| 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
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Protein complex
- Buschdorf, J P.
- Guy, G R.
- Jackson, R A.
- Ng, C.
- Sivaraman, J.
- Sun, Q.
- Atp-binding
- Calcium
- Cbl
- Complex
- Cytoplasm
- Glycoprotein
- Kinase
- Ligase
- Ligase/signaling protein complex
- Membrane
- Metal-binding
- Nucleotide-binding
- Phosphoprotein
- Proto-oncogene
- Receptor
- Sh2 domain
- Signal transduction
- Tkb
- Transferase
- Transmembrane
- Tyrosine-protein kinase
- Ubl conjugation pathway
- Zinc
- Zinc-finger
