Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R.
Researchers at Shanghai Institute of Materia Medica of Chinese Academy of Sciences and ZhejiangUniversity reported a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
The study was published in Nature Communications on August 17. Phd student DUAN Jia at University of Chinese Academy of Sciences (UCAS) (Institute: Shanghai Institute of Materia Medica, Chinese Academy of Sciences) and ZhejiangUniversity), BI Peng and SHEN Dandan at Zhejiang University, and Edward Zhou at Van Andel Institute contributed eqally to the study. Prof. JIANG Yi and Prof. XU Huaqiang at Shanghai Institute of Materia Medica of Chinese Academy of Sciences are the corresponding authors. Prof. JIANG is a master supervisor at UCAS, Prof. XU is a doctoral supervisor at UCAS.
