@article{f913c58a0a13455298bddadf5c43020f,
title = "Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes",
abstract = "The cryo-EM structures of DRD1 coupled to its G protein, in complex with important agonists, elucidates the mechanism of G-protein-coupled selectivity and will facilitate future drug discovery and design.",
keywords = "DRD1-Gs complex, allosteric regulation, catecholamine, ccryo-EM, dopamine receptor, noncatechol, positive allosteric modulator, structure",
author = "Peng Xiao and Wei Yan and Lu Gou and Zhong, {Ya Ni} and Liangliang Kong and Chao Wu and Xin Wen and Yuan Yuan and Sheng Cao and Changxiu Qu and Xin Yang and Yang, {Chuan Cheng} and Anjie Xia and Zhenquan Hu and Qianqian Zhang and He, {Yong Hao} and Zhang, {Dao Lai} and Chao Zhang and Hou, {Gui Hua} and Huanxiang Liu and Lizhe Zhu and Ping Fu and Shengyong Yang and Rosenbaum, {Daniel M.} and Sun, {Jin Peng} and Yang Du and Lei Zhang and Xiao Yu and Zhenhua Shao",
note = "Funding Information: Cryo-EM data were collected at the cryo-EM facility of the National Center for Protein Science in Shanghai. We thank Sichuan University West China Cryo-EM Center and Duyu High Performance Computing Center and the Instrumental Analysis Center of Xi'an Jiaotong University for cryo-EM sample preparation. We thank Professor Yajun Wang, Dr. Jiannan Zhang, and Can Lu from the College of Life Sciences Sichuan University for their help on cAMP measurement. This study was supported by the Science and Technology Department of Sichuan Province (2020YJ0208 to Z.S.), the National Key R&D Program of China (2019YFA0508800 to Z.S. and P.X.), the National Science Fund for Excellent Young Scholars (81822008 to Xiao Yu and 11922410 to Lei Zhang), the National Science Fund for Distinguished Young Scholars (81825022 to J.-P.S.), the National Natural Science Foundation of China (31972916 to Z.S. and 31971195 to P.X.), Shandong University Youth Interdisciplinary Science Innovation Group (2020QNQT002 to Xiao Yu), and the National Institutes of Health (R35GM136387 to D.M.R.). Z.S. initiated the project for DRD1 structural investigation. Z.S. Xiao Yu, Lei Zhang, J.-P.S. and Y.D. supervised the whole project. Z.S. Xiao Yu, and P.X. designed the cellular assays and analyzed results. P.X. Xiao Yu, and J.-P.S. designed the ligand binding experiments. Lei Zhang and L.K. designed the cryo-EM experiments. P.X. W.Y. Y.-N.Z. and X.W. designed the expression constructs, purified the DRD1-Gs-Nb35 complex, prepared the final samples for data collection toward the structures, and participated in figure and manuscript preparation. L.G. L.K. and S.C. prepared the cryo-EM grids and collected cryo-EM images. L.G. performed map calculations under the supervision of Lei Zhang. W.Y. built and refined the structure models. P.X. Y.-N.Z. and C.W. performed binding assay and signaling assays with assistance from Y.Y. C.Q. A.X. C.Z. and G.-H.H. Y.Z. Y.-H.H. and D.-L.Z. performed β-arrestin recruitment assays. Xin Yang, Q.Z. and Z.H. performed the molecular docking and molecular dynamics (MD) simulation under the supervision of S.Y. H.L. and Lizhe Zhu. P.F. D.M.R. Y.D. J.-P.S. and C.-C.Y. helped with data collection, analysis, and manuscript editing. Z.S. J.-P.S. and Xiao Yu wrote the manuscript, with important input from D.M.R. The authors declare no competing interests. Funding Information: Cryo-EM data were collected at the cryo-EM facility of the National Center for Protein Science in Shanghai. We thank Sichuan University West China Cryo-EM Center and Duyu High Performance Computing Center and the Instrumental Analysis Center of Xi{\textquoteright}an Jiaotong University for cryo-EM sample preparation. We thank Professor Yajun Wang, Dr. Jiannan Zhang, and Can Lu from the College of Life Sciences Sichuan University for their help on cAMP measurement. This study was supported by the Science and Technology Department of Sichuan Province ( 2020YJ0208 to Z.S.), the National Key R&D Program of China ( 2019YFA0508800 to Z.S. and P.X.), the National Science Fund for Excellent Young Scholars (81822008 to Xiao Yu and 11922410 to Lei Zhang), the National Science Fund for Distinguished Young Scholars ( 81825022 to J.-P.S.), the National Natural Science Foundation of China ( 31972916 to Z.S. and 31971195 to P.X.), Shandong University Youth Interdisciplinary Science Innovation Group ( 2020QNQT002 to Xiao Yu), and the National Institutes of Health ( R35GM136387 to D.M.R.). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = feb,
day = "18",
doi = "10.1016/j.cell.2021.01.028",
language = "English (US)",
volume = "184",
pages = "943--956.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}