Overall structure of the human Notch1 NRR and comparison with the human Notch2 NRR. (A) Overall structure of the human Notch1 NRR, shown in ribbon representation. Shades of pink and purple represent LNR modules; shades of light and dark cyan, HD domain (on N- and C-terminal sides of the furin cleavage loop, respectively). Disulfide bonds are rendered as yellow sticks, and calcium ions as green spheres. Arrows denote positions of the S1 and S2 cleavage sites. (B) Ribbon representation of the Notch1 NRR colored according to the root mean square deviation (RMSD, in angstroms) between corresponding alpha carbon atoms of the Notch1 and Notch2 structures. Colors are assigned on a sliding scale from blue (RMSD = 0) to red (RMSD = 7.25 Å). Residues present in Notch1 that are absent in Notch2 were set to the maximum RMSD of the range. (C) Overlay of the backbone traces of the Notch1 (colored as in A) and Notch2 (gray) NRRs.