Cbl (CBL)
entry list
alignment
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.