We thank SKLB West China Cryo-EM Center of Sichuan University, Cryo-EM Facility of Westlake University, and Kobilka Cryo-EM Center of the Chinese University of Hong Kong (Shenzhen). We thank Dr. Jiyu Tong for generating hPAC_KO HEK293T cell line and Dr. Li Chen for RNA-seq data analysis. This work was supported by the Natural Science Foundation of Sichuan Province (23NSFSC0123 to D.D.), the National Natural Science Foundation of China (32171211 to D.D., 82271498 to Z.H., 32100979 to X.W.), Science and Technology Innovation 2030-Major Project (2021ZD0202103 to Z.H.) and Ningxia Hui Autonomous Region Key Research and Development Project (2022BEG02042 to Z.H.).