The isolated N‐terminal extracellular domain of the glucagon‐like peptide‐1 (GLP)‐1 receptor has intrinsic binding activity

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Abstract
The glucagon-like peptide 1 (7–37)/(7–36) amide (GLP-1) receptor belongs to a new subclass of seven transmembrane domain, G-protein coupled receptors comprising several receptors for peptide hormones. The receptors of this family share many common motifs including a relatively large N-terminal extracellular domain. The GLP-1 receptor is presently attracting much attention, since it is the target protein of the antidiabetic gut hormone GLP-1. To establish the functional significance of the N-terminal part of the GLP-1 receptor for ligand binding, the extracellular domain was isolated and purified. Utilizing CHL cells expressing the cloned GLP-1 receptor, we demonstrate that the isolated, solubilized N-terminal part of the receptor protein competes for GLP-1 binding with the intact wild-type receptor. Moreover, in cross-linking experiments radiolabeled GLP-1 was covalently attached to the isolated N-terminus, thereby demonstrating direct physical interaction of both components. By Western blot analysis two specific bands were detectable, representing the N-terminal receptor protein in the presence or absence of bound ligand. These data underline the significance of the N-terminal domain of the GLP-1 receptor for ligand binding.

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