title: Structural and molecular conservation of glucagon-like Peptide-1 and its receptor confers selective ligand-receptor interaction.
abstract: 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.
authors.affiliation: Graduate School of Medicine, Korea University Seoul, Republic of Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Moon
authors.forename: Sumi
authors.initials: S
authors.lastname: Park
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Kim
authors.forename: Eun Bee
authors.initials: EB
authors.lastname: Cho
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Hwang
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Seong