New Insulin-Like Proteins with Atypical Disulfide Bond Pattern Characterized in Caenorhabditis elegans by Comparative Sequence Analysis and Homology Modeling

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Abstract
We have identified three new families of insulin homologs inCaenorhabditis elegans. In two of these families, concerted mutations suggest that an additional disulfide bond links B and A domains, and that the A-domain internal disulfide bond is substituted by a hydrophobic interaction. Homology modeling remarkably confirms these predictions and shows that despite this atypical disulfide bond pattern and the absence of C-like peptide, all these proteins may adopt the same fold as the insulin. 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-2insulin-regulating pathway.