The C2, DSL domains and N-terminal EGF repeat in Delta (cyan) and the ligand binding region (EGF11-13) of Notch (magenta) are renditions from the structures obtained (Figure 1), other regions of the molecules are represented not to scale. The amino acids in the β1-2 loop of Delta are highlighted in yellow (A). (A) The interaction of Delta (cyan) in trans with the Notch receptor (magenta) is augmented by the C2 domain, possibly through contacts of the β1-2 loop (yellow), with the "receiving" cell membrane, to yield highest levels of signalling (black arrow; green indicates ligand induced cleavages). Phospholipid contacts from β1-2 loop in the same cell could also influence cis-interactions between Delta and Notch in the same cell. (B) A deletion of 5 amino acids within C2 domain β1-2 loop (no yellow) disrupts phospholipid interactions but does not prevent Delta from interacting with Notch. Activation of Notch signalling is weakened (grey arrow) and phenotypes from transheterozygous combinations suggest that cis-interactions between Delta and Notch are also modulated. 