Conservation of separase N-terminal domain

We report a reanalysis of the sequence conservation of the cell cycle regulatory protease, separase. The sequence and structural conservation of the protease domain has long been recognized. Here we reexamine the protein sequence conservation at the N-terminus using PSI-BLAST analysis and report our discovery of a cysteine rich motif (CxCXXC) conserved in nematodes and vertebrates. This motif is found in a solvent exposed linker region connecting two TPR-like helical motifs. Mutation of this motif in Caenorhabditis elegans separase leads to a temperature sensitive hypomorphic protein, and several N-terminal residues identified as intragenic suppressors are not conserved. Conservation of this motif in multiple organisms raises the possibility that the motif plays similar roles across species.