title: Peptide binding at the GLP-1 receptor.
abstract: 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.
authors.affiliation: Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Mann
authors.forename: N
authors.initials: N
authors.lastname: Nasr
authors.forename: D
authors.initials: D
authors.lastname: Hadden
authors.forename: J
authors.initials: J
authors.lastname: Sinfield
authors.forename: F
authors.initials: F
authors.lastname: Abidi
authors.forename: S
authors.initials: S
authors.lastname: Al-Sabah
authors.forename: R López
authors.initials: RL
authors.lastname: de Maturana
authors.forename: J
authors.initials: J
authors.lastname: Treece-Birch
authors.forename: A
authors.initials: A
authors.lastname: Willshaw
authors.forename: D
authors.initials: D
authors.lastname: Donnelly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D018027:Receptors, Glucagon / Q000235:genetics / Q000502:physiology*
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1