Development of a cysteine-deprived and C-terminally truncated GLP-1 receptor

Christina Rye Underwood, Lotte Bjerre Knudsen, Patrick W. Garibay, Günther H.J. Peters, Steffen Reedtz-Runge

Research output: Contribution to journalJournal articleResearchpeer-review


The glucagon-like peptide-1 receptor (GLP-1R) belongs to family B of the G-protein coupled receptors (GPCRs), and has become a promising target for the treatment of type 2 diabetes. Here we describe the development and characterization of a fully functional cysteine-deprived and C-terminally truncated GLP-1R. Single cysteines were initially substituted with alanine, and functionally redundant cysteines were subsequently changed simultaneously. Our results indicate that Cys174, Cys226, Cys296 and Cys403 are important for the GLP-1-mediated response, whereas Cys236, Cys329, Cys341, Cys347, Cys438, Cys458 and Cys462 are not. Extensive deletions were made in the C-terminal tail of GLP-1R in order to determine the limit for truncation. As for other family B GPCRs, we observed a direct correlation between the length of the C-terminal tail and specific binding of 125I-GLP-1, indicating that the membrane proximal part of the C-terminal is involved in receptor expression at the cell surface. The results show that seven cysteines and more than half of the C-terminal tail can be removed from GLP-1R without compromising GLP-1 binding or function.
Original languageEnglish
Pages (from-to)100-108
Publication statusPublished - 2013


  • G-protein coupled receptor
  • Glucagon-like peptide-1
  • Agonist
  • Cysteine
  • Mutagenesis


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