Fig. 2

3D structural modeling of NOTCH-WT and NOTCH-D1835H. (A) Sequence alignment and secondary structure prediction of NOTCH ANK domains. Multiple sequence alignment of the ANK domain of human NOTCH1–4. The secondary structure assignment of human NOTCH2 is shown above the alignment. Helices are labeled with green cylinder. Red star represents D1853. Residues in red boxes are absolutely conserved; those in yellow boxes are conserved in several of the homologues. (B) 3D structure of NOTCH2 ANK domain (1819–2063 amino acid (aa)). The structure is shown as cartoon (left) and surface (right). (C) 3D structure alignment of NOTCH2-WT (blue) and -D1853H (green) ANK domain. Alignment is shown as cartoon. (D) Close view of 1853 site in the ANK domain. D1853 side chain is shown as blue and H1853 side chain is shown as green. (E) Electrostatic potential of the ANK domain of NOTCH2-WT and -D1853H. WT (left) electrostatic potential is expressed as a spectrum ranging from − 64.5 kT/e (red) to + 64.5 kT/e (blue); D1853H (right) electrostatic potential is expressed as a spectrum ranging from − 57.3 kT/e (red) to + 57.3 kT/e (blue)