Structure of CSL transcription complexes. a) Structure of the human Notch activator complex on DNA (PBD ID: 3v79.1A): CSL (green), Notch 1 ANK-repeats (blue) and the kinked alpha-helical domain of MAML (magenta) (left). Structure prediction of Hydra vulgaris activation complex (right), depicting Notch ANK and CSL, was done by SWISS Model using 3v79.1A as template for human Notch 1 ANK and CSL (center). b) CSL harbors three subdomains, the N-terminal domain NTD, the beta trefoil domain (BTD) and the C-terminal domain (CTD). NTD and BTD contact the DNA (grey). Left: In the activator complex (C. elegans [PDB ID: 2fo1]) Notch makes contacts to the CTD with the ANK domains (yellow), and to the BTD with its RAM domain (red). Mam (light blue) contacts BTD and ANK. Middle: The CSL-ID of KyoT2 (pink) (PDB-ID: 4J2X) makes very similar contacts as RAM with the BTD. Right: In contrast, contacts between fly Hairless (pink) and Su(H) are restricted to the CTD only (PDB ID: 5E24). c) Sequence comparison of the CSL-interacting domain from KyoT2, RITA and EBNA2 with RAM domains of Notch [Hydra vulgaris (Hv Notch), Homo sapiens (Hs Notch1), Drosophila melanogaster (Dm Notch), Caenorhabditis elegans (Ce LIN-12)]. Note lack of the typical ΦWΦP motif in Hydra Notch (Φ, any hydrophobic residue). d) Simplified phylogenetic tree of chordates and arthropods. Red: branches with SHARP coding genes, blue: with Hairless coding genes