Cbl (CBL)

entry list
CBL binds to phosphorylated tyrosine residues and functions as a negative regulator of many signaling pathways. The crystal structure [86] of CBL (minus residues 1 - 24) alone and in complex with a phosphotyrosine decapeptide that represents its binding site in ZAP-70 shows the pair of EF-hands wedged between a four helix bundle (4HB) and a divergent SH2 domain. The coordination of Ca2+ is unique as indicated in table 1 by "d". Although the residue at -X is Ser, the -X oxygen ligand comes from the carboxylate group of a Glu from the fourth helix of the 4HB. Although calcium is required for phosphopeptide binding, it interacts with the SH2 domain, not the pair of EF-hands. The pair of EF-hands may position the 4HB relative to the SH2 domain.