Comparison of NCS-1 orthologues and identification of residues for targeted mutation. (A) There is extensive homology between human, C. elegans and S. cerevisiae NCS-1 orthologues. Identical residues in all three species are shaded in blue and those with similarity across species are shaded in red. (B) Hydrophobic residues implicated in target protein interactions are conserved in C. elegans NCS-1. Then residues that directly make contact with target proteins in structurally characterised complexes are indicated above the sequence of C. elegans NCS-1. Residues selected for mutagenesis are boxed. (C) Position of residues selected for mutagenesis in the predicted NCS-1 structure. The selected amino acids are within the hydrophobic groove are shown in red in a surface representation of model structures for C. elegans NCS-1 based on the crystal structure of human NCS-1 (PDB1G8I, left) or the solution NMR structure (PDB 2LCP, right). In the structure predicted from the NMR structure V125 is not surface exposed but buried beneath the C-terminal tail and so not visible in the figure.