Nature: scientists unveil the reality of type B G protein coupled receptor

Scientists from Scripps Research Institute of the United States and Shanghai Institute of medicine of Chinese Academy of Sciences and other research institutions first analyzed the three-dimensional molecular structure of the seven transmembrane region of glucagon receptor in the world, thus changing the long-standing dilemma in the research of the structure of B-type G protein coupled receptor This is an important research achievement made by Chinese scientists as one of the main researchers in clarifying the molecular structure of drug targets for major diseases With this achievement, researchers are expected to design and develop new oral drugs for the treatment of type 2 diabetes The research was published online in nature recently According to the news review published in nature, the successful analysis of the transmembrane structure of these two receptors 7 times is a major breakthrough in the field of G protein coupled receptor research According to reports, G protein coupled receptors can be divided into six types: A, B, C, D, e and F about 40% of modern drugs target these receptors Since the first three-dimensional molecular structure of G-protein-coupled receptor was cracked, scientists have analyzed more than 20 G-protein-coupled receptors, but all of them belong to type A From the point of view of the importance of maintenance of life activities, the role of B-type G protein coupled receptor can not be ignored, but due to its complex structure, the molecular face of B-type receptor has not been revealed This time, the researchers obtained the protein crystal of the transmembrane region of glucagon receptor 7 times with a resolution of 3.4 angstroms, and constructed the structural model of molecular recognition between the receptor and glucagon The results show that the binding pocket of glucagon receptor is larger than that of A-type G-protein-coupled receptor The first transmembrane helix extends three α helices out of the cell membrane, forming a "stem" like structure to "capture" glucagon and insert its amino end into the transmembrane region to bind to the receptor Wang Mingwei, an expert of the national "thousand talents plan" and a researcher of Shanghai Institute of medicine, Chinese Academy of Sciences, is one of the leaders of the study He told reporters that glucagon and insulin have the opposite effect, which can increase blood sugar in the body Therefore, after analyzing the structure of the receptor, it is expected to design and develop more targeted anti type 2 diabetes drugs.