Structure of mGlu Photo by the Research Group
Chinanews.com, Hangzhou, June 21 (Huang Lingyi) On June 21, the reporter learned from Hangzhou Institute for Advanced Study (HIAS), UCAS that Wu Beili's Research Group, Zhao Qiang's Research Group, Wang Mingwei's Research Group, and Liu Hong's Research Group of the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences (CAS), including several double-employed professors from HIAS School of Pharmaceutical Science and Technology, together with Sun Fei's Research Group of the Institute of Biophysics, CAS and Liu Jianfeng's Research Group of Huazhong University of Science and Technology, have made a series of important advances in the study of the structure and function of Class C GPCR. Their two related research papers have been published online "back to back" in Nature, the top international academic journal, which is of great significance to the creation of new drugs for mental and nervous system diseases.
The 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 co-first authors of the former are Du Juan, postdoctoral fellow of HIAS, Wang Dejian and Lin Shuling, doctoral students of the Shanghai Institute of Materia Medica of CAS, Fan Hongcheng and Tai Linhua, doctoral students of the Institute of Biophysics, CAS, and Xu Chanjuan, lecturer of Huazhong University of Science and Technology.
The mGlu belongs to the C-GPCR family and is one of the most important neurotransmitter receptors in the human body. At present, a total of 8 kinds of mGlu (mGlu1-8) have been identified in the human body. Their functions are related to learning, memory, emotions, pain perception, and so on. They serve as therapeutic targets for Alzheimer’s disease and schizophrenia. However, drugs targeting the mGlus are not currently available, so the research of their structure and function is of great significance for the development of new drugs treating neurological and psychiatric disorders.
According to related researchers, compared with other types of GPCR, Class C GPCR such as mGlu has a unique activation mechanism, and receptors must form homologous or heterodimers to function. However, it has long been unclear how different types of dimerization modulate receptor activation and how these receptors activate intracellular effector proteins such as G proteins.
The researchers said that the studies, for the first time, offered a thorough view of receptor conformational changes during the whole process of mGlu activation from inactive to fully activate states, and reveal the complex signal transduction patterns of their homo- and heterodimers, providing an important basis for a deeper understanding of the functional regulation mechanism of these receptors in the central nervous system. It is of great significance to comprehensively understand the signal transduction of class C GPCR.
It is reported that another breakthrough in this study is the first to provide a direct basis for studying the asymmetric activation of mGlus. In addition, the joint research group also explored the dimeric association and functional regulation mechanism of mGlu heterodimer. (The End)
Executive Editor | Tian Boqun
