Fig. 3

Uncoupled evolution of Notch-1 ankyrin domain from other functional domains of the receptor. a Alignment of the primary sequence of EGF, RAM, and ANK domains of human Notch-1 and Drosophila N reveals high conservation of ANK domain despite significant divergence of the EGF and RAM domains (See Additional file 1: Fig. S1). b, c Comparison of the primary sequence of human Notch-1 (hs-Notch1) and D. melanogaster N (Dm-N) to S. cerevisiae Swi-6 shows marked enrichment of alanine, with the highest propensity for helix formation (42), in α-helices of Notch ankyrin domain. A second important structural adaption of Notch ankyrin domain was enrichment of acidic amino acids with negative side chains in solvent exposed surface of α-helices and β-hairpins