Structural and molecular conservation of glucagon-like peptide-1 and its receptor confers selective ligand-receptor interaction

초록

Glucagon-like peptide-1 (GLP-1) is a major player in the regulation of glucose homeostasis. It acts on pancreatic beta cells to stimulate insulin secretion and on the brain to inhibit appetite.Thus, it may be a promising therapeutic agent for the treatment of type 2 diabetes mellitus and obesity. Despite the physiological and clinical importance of GLP-1, molecular interaction with the GLP-1 receptor (GLP1R) is not well understood. Particularly, the specific amino acid residues within the transmembrane helices and extracellular loops of the receptor that may confer ligand-induced receptor activation have been poorly investigated. Amino acid sequence comparisons of GLP-1 and GLP1R with their orthologs and paralogs in vertebrates, combined with biochemical approaches, are useful to determine which amino acid residues in the peptide and the receptor confer selective ligand-receptor interaction. This article reviews how the molecular evolution of GLP-1 and GLP1R contributes to the selective interaction between this ligand-receptor pair, providing critical clues for the development of potent agonists for the treatment of diabetes mellitus and obesity. © 2012 Moon, Park, Kim, Cho, Hwang, Vaudry and Seong.

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