title: A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor.
abstract: Caenorhabditis elegans contains a family of putative insulin-like genes proposed to regulate dauer arrest and senescence. These sequences often lack characteristic sequence features of human insulin essential for its folding, structure, and function. Here, we describe the structure and receptor-binding properties of INS-6, a single-chain polypeptide expressed in specific neurons. Despite multiple nonconservative changes in sequence, INS-6 recapitulates an insulin-like fold. Although lacking classical receptor-binding determinants, INS-6 binds to and activates the human insulin receptor. Its activity is greater than that of an analogous single-chain human insulin analog.
authors.affiliation: Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Qing-Xin
authors.initials: QX
authors.lastname: Hua
authors.forename: Satoe H
authors.initials: SH
authors.lastname: Nakagawa
authors.forename: Jill
authors.initials: J
authors.lastname: Wilken
authors.forename: Rowena R
authors.initials: RR
authors.lastname: Ramos
authors.forename: Wenhua
authors.initials: W
authors.lastname: Jia
authors.forename: Joseph
authors.initials: J
authors.lastname: Bass
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000502:physiology*; D008322:Mammals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011972:Receptor, Insulin / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates
chemical_list: D007328:Insulin; D011972:Receptor, Insulin