The receptor for GLP-1 [glucagon-like peptide-1-(7–36)-amide] is a member of the ‘Family B’ of GPCRs (G-protein-coupled receptors) comprising an extracellular N-terminal domain containing six conserved cysteine residues (the N-domain) and a core domain (or J-domain) comprising the seven transmembrane helices and interconnecting loop regions. According to the two-domain model for peptide binding, the N-domain is primarily responsible for providing most of the peptide binding energy, whereas the core domain is responsible for binding the N-terminal region of the peptide agonists and transmitting the signal to the intracellular G-protein. Two interesting differences between the binding properties of two GLP-1 receptor agonists, GLP-1 and EX-4 (exendin-4), can be observed. First, while GLP-1 requires its full length to maintain high affinity, the eight N-terminal residues of EX-4 can be removed with little reduction in affinity. Secondly, EX-4 (but not GLP-1) can bind to the fully isolated N-domain of the receptor with an affinity matching that of the full-length receptor. In order to better understand these differences, we have studied the interaction between combinations of full-length or truncated ligands with full-length or truncated receptors.
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August 2007
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Conference Article|
July 20 2007
Peptide binding at the GLP-1 receptor
R. Mann;
R. Mann
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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N. Nasr;
N. Nasr
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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D. Hadden;
D. Hadden
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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J. Sinfield;
J. Sinfield
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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F. Abidi;
F. Abidi
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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S. Al-Sabah;
S. Al-Sabah
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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R. López de Maturana;
R. López de Maturana
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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J. Treece-Birch;
J. Treece-Birch
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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A. Willshaw;
A. Willshaw
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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D. Donnelly
D. Donnelly
1
1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
1To whom correspondence should be addressed (email d.donnelly@leeds.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 30 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 713–716.
Article history
Received:
March 30 2007
Citation
R. Mann, N. Nasr, D. Hadden, J. Sinfield, F. Abidi, S. Al-Sabah, R. López de Maturana, J. Treece-Birch, A. Willshaw, D. Donnelly; Peptide binding at the GLP-1 receptor. Biochem Soc Trans 1 August 2007; 35 (4): 713–716. doi: https://doi.org/10.1042/BST0350713
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