A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor

Qing xin Hua, Satoe H. Nakagawa, Jill Wilken, Rowena R. Ramos, Wenhua Jia, Joseph Bass, Michael A. Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Scopus citations

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 singlechain 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.

Original languageEnglish (US)
Pages (from-to)826-831
Number of pages6
JournalGenes and Development
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2003

Keywords

  • Hormone
  • Metabolism
  • NMR
  • Protein evolution
  • Protein structure
  • Senescence

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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