Domain organization and multiple sequence alignment. (A) Domain organization of human Notch1. The NRR consists of the LNR and HD domains. Adapted from Gordon et al.⁴⁰  (B) Sequence alignment of the NRR region of various Notch receptors, colored according to sequence conservation: red indicates absolutely conserved; orange, highly conserved (defined by ClustalW⁴¹  strong conservation groups and/or > 80% sequence identity); yellow, moderately conserved (defined by ClustalW weak conservation groups or > 50% sequence identity); and white, nonconserved. Amino acid residues of special importance are denoted as follows: side-chain and main-chain Ca⁺⁺-coordinating residues, circles and triangles, respectively; residues mutated in Notch1 in T-ALL, asterisks. Residues from LNR-C engaged in crystal lattice contacts are boxed. Representative disulfide connectivity is shown for LNR-A and HD secondary structural elements are represented by arrows (beta strands) and cylinders (alpha helices).