China News Service, Hangzhou, June 21 (Huang Lingyi) A reporter learned from the National University of Science and Technology Hangzhou Institute of Advanced Studies on the 21st that the Wu Beili research group of the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, including multiple double-appointed professors from the School of Pharmacy of the Institute, Zhao Qiang's research group, Wang Mingwei's research group, and Liu Hong's research group joined forces with Sun Fei's research group at the Institute of Biophysics, Chinese Academy of Sciences and Liu Jianfeng's research group at Huazhong University of Science and Technology. They have achieved research in the structure and function of class C G protein-coupled receptors (GPCRs) A series of important developments have been made. Two related research papers have been published online "back-to-back" in the top international academic journal "Nature" a few days ago, which are of great significance to the creation of new drugs for neuropsychiatric diseases.
Two papers are entitled "Structures of human mGlu2 and mGlu7 homo-and heterodimers" and "Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4".
Among them, the former co-first authors are Du Juan, postdoctoral fellow at Hangzhou Institute of Advanced Studies, National University of Science and Technology; Wang Dejian and Lin Shuling, doctoral students at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences; Fan Hongcheng and Tai Linhua, doctoral students at the Institute of Biophysics, Chinese Academy of Sciences; and Xu Chanjuan, lecturer at Huazhong University of Science and Technology .
Metabotropic glutamate receptor (mGlu) belongs to the C-type GPCR family and is one of the most important neurotransmitter receptors in the human body.
At present, 8 metabotropic glutamate receptors (mGlu1-8) have been found in the human body. Their functions involve learning, memory, mood, and pain perception, etc., and are therapeutic targets for diseases such as Alzheimer’s and schizophrenia. point.
However, no drugs targeting this type of receptor have been successfully marketed so far, so the study of its structure and function is of great significance for the creation of new drugs for neuropsychiatric diseases.
According to related researchers, compared with other types of GPCRs, class C GPCRs such as mGlu have a unique activation mechanism, and receptors must form homologous or heterodimers to perform their functions.
However, the regulation mechanism of different types of dimerization on receptor activity and how this type of receptor activates intracellular effectors such as G protein has been unclear for a long time.
The above-mentioned researchers stated that the significance of the results of this study is that this is the first comprehensive explanation of the fine conformational change process of metabotropic glutamate receptors from inactive to fully activated state, and reveals their homology and heterologous. The complex signal transduction mode of dimers provides an important basis for in-depth understanding of the functional regulation mechanism of this type of receptor in the central nervous system, and is of great significance for a comprehensive understanding of the signal transduction mechanism of class C GPCRs.
It is reported that another breakthrough of the study is the first to provide a direct basis for studying the asymmetric activation mechanism of metabotropic glutamate receptors.
In addition, the joint research team also explored the assembly and functional regulation mechanisms of mGlu heterodimers.
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