Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain

A tracer competition assay and ligand-induced thermal stabilization of nGLP-1R was used to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The results show that the Trp-cage plays only a minor role for the interaction between exendin-4 (Ex4) and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.