Please use this identifier to cite or link to this item:
|Title:||Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates|
|Citation:||Ng, C., Jackson, R.A., Buschdorf, J.P., Sun, Q., Guy, G.R., Sivaraman, J. (2008-03-05). Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates. EMBO Journal 27 (5) : 804-816. ScholarBank@NUS Repository. https://doi.org/10.1038/emboj.2008.18|
|Abstract:||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. © 2008 European Molecular Biology Organization | All Rights Reserved.|
|Source Title:||EMBO Journal|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jun 21, 2018
WEB OF SCIENCETM
checked on May 9, 2018
checked on May 18, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.