Journal article
Development of a cysteine-deprived and C-terminally truncated GLP-1 receptor
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.
| Language: | English |
|---|---|
| Year: | 2013 |
| Pages: | 100-108 |
| ISSN: | 18735169 and 01969781 |
| Types: | Journal article |
| DOI: | 10.1016/j.peptides.2013.09.001 |
| ORCIDs: | Peters, Günther H.J. |
Agonist Cysteine G-protein coupled receptor Glucagon-like peptide-1 Mutagenesis SDG 3 - Good Health and Well-being
Amino Acid Sequence CLR CRFR1 ECL FRET GCGR GIP-R GLP-1 GLP-1R GLP1R protein, human GPCR Glucagon-Like Peptide-1 Receptor HEK293 Cells Humans ICL JNK1 Molecular Sequence Data PAC1-R PTH-1R PTHrP Receptors, Glucagon Sequence Homology, Amino Acid TM VIP c-Jun N-terminal Kinase 1 calcitonin receptor-like receptor extracellular loop fluorescence resonance energy transfer glucagon receptor glucagon-like peptide-1 glucagon-like peptide-1 receptor glucose-dependent insulinotropic polypeptide receptor intracellular loop parathyroid hormone related peptide transmembrane type-1 corticotrophin-releasing factor receptor type-1 parathyroid hormone receptor type-1 pituitary adenylate cyclase-activating polypeptide receptor vasoactive intestinal polypeptide β(1/2)-adreneric receptor β(1/2)AR
