Scientists unveil the true face of type B G protein coupled receptors

Scientists from the Scripps Research Institute in the United States and the National Center for New Drug Screening in China, Shanghai Institute of Pharmaceutical Sciences, Chinese Academy of Sciences and other research institutions have for the first time internationally resolved the three-dimensional molecular structure of the glucagon receptor 7 transmembrane region, which has changed The long-term difficulties encountered in the study of the structure of B-type G protein coupled receptors. This is a major research achievement made by Chinese scientists as one of the main researchers in elucidating the molecular structure of drug targets of major diseases. Using this achievement, researchers are expected to design and develop new oral drugs for the treatment of type 2 diabetes. "Nature" magazine recently published the research results online.

According to a news review published by Nature, the successful analysis of the seven-time transmembrane domain structure of these two receptors is a major breakthrough in the field of G protein-coupled receptor research.

According to reports, G protein-coupled receptors are divided into six types: A, B, C, D, E, and F. About 40% of modern drugs target these receptors. Since cracking the first three-dimensional molecular structure of the G protein-coupled receptor, scientists have resolved more than 20 G protein-coupled receptors, but the ones that have been resolved so far belong to type A. From the perspective of the importance of maintaining life activities, the role of the B-type G protein-coupled receptor cannot be ignored, but because of the very complex structure, the molecular face of the B-type receptor has not been revealed.

The researchers obtained protein crystals of the transmembrane region of the glucagon receptor with a resolution of 3.4 angstroms seven times, and constructed a structural model for molecular recognition of the receptor and glucagon. Studies have shown that glucagon receptors have a larger "pocket" of ligand binding than type A G protein-coupled receptors, and the first transmembrane helix extends 3 alpha helixes outside the cell membrane, forming " The stem-like structure is used to "capture" glucagon so that its amino terminus is inserted into the transmembrane region to bind to the receptor.

Wang Mingwei, an expert in the National Thousand Talents Program and a researcher at the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, is one of the leaders in the study. He told reporters that glucagon and insulin have the opposite effect and can raise blood sugar in the body. Therefore, after analyzing the structure of this receptor, it is expected to design and develop more targeted anti-type 2 diabetes drugs.

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