THE ISOLATED N-TERMINAL EXTRACELLULAR DOMAIN OF THE GLUCAGON-LIKE PEPTIDE-1 (GLP)-1 RECEPTOR HAS INTRINSIC BINDING-ACTIVITY

The glucagon-like peptide 1 (7-37)/(7-36) amide (GLP-1) receptor belon gs to a new subclass of seven transmembrane domain, G-protein coupled receptors comprising several receptors for peptide hormones. The recep tors of this family share many common motifs including a relatively la rge N-terminal extracellular domain, The GLP-1 receptor is presently a ttracting much attention, since it is the target protein of the antidi abetic gut hormone GLP-1. To establish the functional significance of the N-terminal part of the GLP-1 receptor for ligand binding, the extr acellular domain was isolated and purified, Utilizing CHL cells expres sing the cloned GLP-1 receptor, we demonstrate that the isolated, solu bilized N-terminal part of the receptor protein competes for GLP-1 bin ding with the intact wild-type receptor, Moreover, in crosslinking exp eriments radiolabeled GLP-1 was covalently attached to the isolated N- terminus, thereby demonstrating direct physical interaction of both co mponents. By Western blot analysis two specific bands were detectable, representing the N-terminal receptor protein in the presence or absen ce of bound ligand. These data underline the significance of the N-ter minal domain of the GLP-1 receptor for ligand binding.