title: New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.
abstract: We have identified three new families of insulin homologs in Caenorhabditis 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-2 insulin-regulating pathway.
authors.affiliation: Laboratoire BGBP-UMR Centre National de la Recherche Scientifique (CNRS) 5558, Université Claude Bernard - Lyon 1, F-69622 Villeurbanne Cedex, France. duret@biomserv.univ-lyon1.fr
authors.forename: L
authors.initials: L
authors.lastname: Duret
authors.forename: N
authors.initials: N
authors.lastname: Guex
authors.forename: M C
authors.initials: MC
authors.lastname: Peitsch
authors.forename: A
authors.initials: A
authors.lastname: Bairoch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000235:genetics; D004220:Disulfides / Q000737:chemistry*; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D015801:Helminth Proteins; D007328:Insulin