New Insulin-Like Proteins with Atypical Disulfide Bond Pattern Characterized in Caenorhabditis elegans by Comparative Sequence Analysis and Homology Modeling
- 1Laboratoire BGBP–UMR Centre National de la Recherche Scientifique (CNRS) 5558, Université Claude Bernard - Lyon 1, F-69622 Villeurbanne Cedex, France; 2Geneva Biomedical Research Institute, Glaxo-Wellcome, CH-1228 Plan-les-Ouates, Switzerland; 3Département de Biochimie Médicale, CH-1211 Geneva 4, Switzerland
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.
Footnotes
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↵4 Corresponding author.
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E-MAIL duret{at}biomserv.univ-lyon1.fr; FAX 33 4 78 89 27 19.
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- Received November 18, 1997.
- Accepted February 17, 1998.
- Cold Spring Harbor Laboratory Press
