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The use of GLP-1/glucagon chimaeric ligands, coupled with site-directed mutagenesis of the glucagon receptor, has shown that the reduced activity of an analogue of glucagon, with Ala at position 2, could be rescued by mutating Asp 385 to Glu, suggesting that the N-terminus binds close to the TM7/ECL3 boundary (Runge et al
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