The cross-cutting team led by Xu Huaqiang, a researcher at the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences, jointly attacked the major scientific problems in the field of cell signal transduction by successfully analyzing the near-atomic resolution structure of Rhodopsin and the inhibitory G protein (Gi) complex using cryoscopic electron sclier technology.
's breakthrough was published online in the international academic journal Nature on June 14, Beijing time.
GPCR is the largest class of cell transmembrane signal transduction receptor family and the most important drug target, which transduces extracellular signals through a variety of effect proteins, such as the conjugated downstream G protein and the deterrent protein.
in a variety of GPCR-effect proteins, the inhibitory G protein (Gi) can selectively conjugate GPCrs such as serotonin receptors and dopamine receptors, and play functions such as regulating mood, appetite, motivation, cognition and reward.
Xu Huaqiang's team made a major breakthrough in the field of THE structure of GPCR and Gi protein complex, and obtained the near-atomic resolution frozen electron mirror structure of the visual reclusive and Gi protein complexes.
the structure shows the structural details of the interface between GPCR and Gi protein for the first time, perfects the understanding of the selective molecular mechanism of GPCR-Gi downstream transduction, and also provides a structural biological basis for the design of efficient and low-toxic GPCR targeted drugs.
this work is another important breakthrough in the field of GPCR research between Xu Huaqiang and his co-operatives.
2015, using X-ray free electron laser technology, published the crystal structure of rhodopsin and inhibitor protein complexes in the journal Nature in 2015, tackling major scientific challenges in the field of cell signal transduction.
this breakthrough was selected by the two academicians to select the top ten scientific and technological progress news in China in 2015, and Xu Huaqiang was awarded the Hans Neurath Award by the International Protein Society in 2016.
2017, using the strongest X-ray laser again to crack the phosphorylation code for GPCR recruiting inhibitors, published in a cover article in the journal Cell.
these research results, the interaction between GPCR and downstream multi-effect proteins is studied in depth and systematically, and the molecular mechanism of GPCR signaling pathway transduction is expounded, which is of great theoretical significance and practical application value.
the work was carried out in collaboration with the Shanghai Institute of Drugs, the Winanlo Institute, the Frederick National Cancer Research Laboratory in the United States, the University of Chicago, the University of Toronto, Canada, and the National Cancer Institute. In addition to international project support, the
study was supported by projects such as the National Natural Fund Commission.