Fig. 4. Ribbon diagrams representing the structure of human and worm Notch ternary complexes. (A, left) Human complex of the ANK domain of NOTCH1 (blue), CSL (green) and the N-terminal region of MAML1 (red) bound to an 18 base-pair DNA sequence from the hes1 promoter (PDB code 2F8X). (A, right) Worm complex of the RAMANK region of LIN-12 (ANK and RAM are blue and cyan, respectively), LAG-1 (green), and the N-terminal region of SEL-8 (red) (PDB code 2FO1). The structures illustrate the cooperative binding of MAM to a composite surface that is created at the interface between the Notch ANK domain and CSL. Bottom panels show a 105° rotation around the vertical axis. (B) Superposition of CSL structures, showing the difference in loop conformation between CSL-DNA complexes and complexes that include RAM domains, ANK domains or both. Mouse CSL-DNA (PDB code 3BRG, magenta) and worm CSL-DNA (PDB code 1TTU, green) structures have a `closed' loop. Worm RAM-CSL-DNA (PDB code 3BRF, yellow; PDB code 3BRD, cyan), human ANK-MAM-CSL-DNA (red) and worm RAMANK-MAM-CSL-DNA (blue) complexes have an `open' loop. (C) Superposition of worm (bright) and human (faded) ternary-complex structures. Several unique insertions at the N-terminus of RAM and within the ANK domain are found in worm LIN-12 but not in other Notch molecules (orange). These features might play a role in the more compact packing of the worm NTC structure when compared with the human NTC structure.