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

Mi Jin Moon, Sumi Park, Dong Kyu Kim, Eun Bee Cho, Jong Ik Hwang, Hubert Vaudry, Jae Young Seong

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish
Article numberArticle 141
JournalFrontiers in Endocrinology
Volume3
Issue numberNOV
DOIs
Publication statusPublished - 2012

Keywords

  • Evolution
  • G protein-coupled receptors
  • GLP-1
  • GLP1R
  • Ligand-receptor interaction
  • Ortholog
  • Paralog

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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