NEW INSULIN-LIKE PROTEINS WITH ATYPICAL DISULFIDE BOND PATTERN CHARACTERIZED IN CAENORHABDITIS-ELEGANS BY COMPARATIVE SEQUENCE-ANALYSIS ANDHOMOLOGY MODELING

We have identified three new families of insulin homologs in Caenorhab ditis elegans. In two of these families, concerted mutations suggest t hat an additional disulfide bond links B and A domains, and that the A -domain internal disulfide bond is substituted by a hydrophobic intera ction. Homology modeling remarkably confirms these predictions and sho ws that despite this atypical disulfide bond pattern and the absence o f C-like peptide, all these proteins may adopt the same fold as the in sulin. Interestingly, whereas we identified 10 insulin-like peptides, only one insulin-like-receptor (daf-2) has been found. We propose that these insulin-related peptides may correspond to different activators or inhibitors of the daf-2 insulin-regulating pathway.