Ligand binding triggers the proteolytic cleavage of NOTCH receptors, whichis mediated by distinct enzymes []. Jagged-1 (JAG2) is a ligand for the Notch receptors []. The Jagged-Notch signalling plays important roles in the maintenance of proliferating neural precursors [, ]and in kidney development [].
The REP domain of Mind bomb which serves as the substrate recognition domain for a second, membrane-distal epitope of the Notch ligand (C-box). Although the first Mib repeat of REP may play a dominant role in ligand binding, the two repeats appear to cooperate in the engagement of the Jag1 tail. Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. The structure and functional analysis, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. REP domains have a five-stranded anti-parallel twisted beta sheet topology similar to that of SH3 domains [].
