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3buw
From Proteopedia
| 3buw, resolution 1.45Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Non-Standard Residues: | |||||||||
| Gene: | CBL, CBL2, RNF55 (Homo sapiens) | ||||||||
| Domains: | Cbl_N3, Cbl_N2, Cbl_N | ||||||||
| Related: | 3bum, 3bun, 3buo, 3bux | ||||||||
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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 Syk
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3BUW is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J. Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates. EMBO J. 2008 Mar 5;27(5):804-16. Epub 2008 Feb 14. PMID:18273061 doi:10.1038/emboj.2008.18
Page seeded by OCA on Mon Feb 16 16:24:27 2009
Categories: Homo sapiens | Buschdorf, J P. | Guy, G R. | Jackson, R A. | Ng, C. | Sivaraman, J. | Sun, Q. | Alternative splicing | Atp-binding | Calcium | Cbl | Complex | Cytoplasm | Host-virus interaction | Kinase | Ligase | Ligase/signaling protein complex | Metal-binding | Nucleotide-binding | Phosphoprotein | Polymorphism | Proto-oncogene | Sh2 domain | Signal transduction | Tkb | Transferase | Tyrosine-protein kinase | Ubl conjugation | Ubl conjugation pathway | Zinc | Zinc-finger
