Wang Mingwei group of Shanghai Institute of medicine, Chinese Academy of Sciences has made new progress in the study of the structure and function of glucagon like peptide-1 receptor

G-protein coupled receptor is a family of membrane proteins with seven transmembrane structures Glucagon like peptide-1 receptor belongs to B1 type, which is the treatment target of type 2 diabetes and obesity There are nearly ten kinds of receptor agonists on the market, including exenatide, lilalutide and dulaglutide, with an annual sales volume of more than 10 billion US dollars The different administration frequency, clinical efficacy, adverse reactions and tolerance of these drugs are closely related to the biased excitatory effect of glucagon like peptide-1 Wang Mingwei group of Shanghai Institute of medicine, Chinese Academy of Sciences, together with Patrick Sexton and Denise Wootten group of Monash University, Australia, began to organize joint research three years ago 28 amino acids in the N-terminal and the first transmembrane helix extracellular domain of the receptor were mutated at a specific point A variety of techniques were used to systematically study the mutations The affinity of various peptide ligands to receptors and the activation efficiency of different signaling pathways (camp, pERK1 / 2 and Ca2 +) The results showed that glucagon like peptide-1 Different amino acid sites on the receptor regulate the affinity of the ligand and the signal pathway it activates There are both similarities and characteristics between the ligands and the signal pathway, indicating that the domain plays an important role in the regulation of signal biased transduction, which provides a new idea for the design of drugs based on the principle of receptor biased activation The cooperative research results were published on the Journal of Biological Chemistry (DOI: 10.1074 / JBC Ra118.003278) under the title of "two distinct domains of the glucose like peptide-1 receptor control peptide mediated Bian agriculture" The research was supported by the national health and Medical Research Commission of Australia, the National Natural Science Foundation, the strategic leading science and technology program of the Chinese Academy of Sciences and the Shanghai Science and technology development fund Wang Mingwei, the first author of the paper, was a doctoral student of the research group, Lei Saifei, who went to Australia to study under the support of the joint doctoral training program of the Chinese Academy of Sciences.