A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor.
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.
Hua
Qing-Xin
QX
Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA.
Nakagawa
Satoe H
SH
Wilken
Jill
J
Ramos
Rowena R
RR
Jia
Wenhua
W
Bass
Joseph
J
Weiss
Michael A
MA
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
D007328:Insulin; D011972:Receptor, Insulin