Structural Biology Of Human Metabotropic Glutamate Receptor-1 (mGlu1)

Metabotropic glutamate receptor(mGlu)is a group of G protein-coupled receptor C family and is involved in many physiological and pathological processes in the human body.Glutamate is the main excitatory neurotransmitter,so metabotropic glutamate receptors have been implicated in many central nervous system diseases.Recently,the incidence rate of many kinds of central nervous system diseases is increasing,but the existing drugs are single and have many serious side effects.Therefore,metabotropic glutamate receptor is a very attractive new drug target.The analysis of full-length structure of high-resolution human mGlu1 could provide structural basis for the research of drugs targeting mGlu1,and can give perspective to understand activation mechanism.In order to analyze the structure of human mGlu1 with high resolution,this study used mammalian expression system to screen different clones and optimized protein expression and purification conditions to increase protein yield,and screened different detergent to improve protein stability and resolution,and finally obtain high-purity human mGlu1 protein.At the same time,we have successfully assembled mGlu1 protein in the nanodiscs.In this study,we obtain cryoelectron microscopy data of mGlu1 in nanodiscs.The current data show that it is possible to obtain full-length human mGlu1 structure with high resolution after successful data analysis.