刘翔宇 博士

助理教授

主要科研领域与方向

G蛋白偶联受体（GPCR）是一类具有七次跨膜螺旋的膜蛋白受体，它们感知多种不同胞外信号，调节细胞对环境的反应。其配体包括激素、神经递质、趋化因子等。目前已上市的药物约三分之一靶向GPCR。在过去的十多年，针对GPCR的结构生物学研究取得了巨大的进展，但是对GPCR-G蛋白特异性识别的机理，GPCR偏向性信号传导的机理尚不清楚。本实验室关注与疾病相关的重要GPCR的结构生物学研究，以及基于结构的药物设计。另外，我们也关注新的GPCR药物筛选方法的研发。

代表性论文

1.     Xiuqing Lv^#, Kaixuan Gao^#, Jia Nie^#, Xin Zhang, Shuhao Zhang, Yinhang Ren, Xiaoou Sun, Qi Li, Jingrui Huang, Lijuan Liu, Xiaowen Zhang, Weishe Zhang*, Xiangyu Liu*. Structures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity. Nature Communications. (2023) 14 (1):8136. doi: 10.1038/s41467-023-43922-8.

2.     Xinyu Xu, Jeremy Shonberg, Jonas Kaindl, Mary J. Clark, Anne Stößel, Luis Maul, Daniel Mayer, Harald Hübner, Kunio Hirata, A. J. Venkatakrishnan, Ron O. Dror, Brian K. Kobilka*, Roger K. Sunahara*, Xiangyu Liu*, Peter Gmeiner*. Constrained catecholamines gain β2AR selectivity through allosteric effects on pocket dynamics. Nature Communications. (2023) 14, 2138.

3.     Xinyu Xu^#, Jonas Kaindl^#, Mary J. Clark^#, Harald Hübner, Kunio Hirata, Roger K. Sunahara*, Peter Gmeiner*, Brian K. Kobilka, Xiangyu Liu*. (2021) Binding pathway determines norepinephrine selectivity for the human β1AR over β2AR. Cell Research. 31, 569-579.

4.     Xiangyu Liu^#, Jonas Kaindl^#, Magdalena Korczynska, Anne Stößel, Daniela Dengler, Markus Stanek, Harald Hübner, Jake Mahoney, Mary J. Clark, Rachel Ann Matt, Xinyu Xu, Kunio Hirata, Brian K. Shoichet, Roger K. Sunahara*, Brian K. Kobilka*, Peter Gmeiner*. (2020) Discovery of an allosteric modulator binding to a conformational hub in the β2 adrenergic receptor. Nature Chemical Biology. 16, 749-755.

5.     Xiangyu Liu^#, Ali Masoudi^#, Alem W. Kahsai^#, Li-Yin Huang, Biswaranjan Pani, Dean P. Staus, Paul J. Shim, Kunio Hirata, Rishabh K. Simhal, Allison M. Schwalb, Paula K. Rambarat, Seungkirl Ahn, Robert J. Lefkowitz*, Brian Kobilka*. (2019) Mechanism of β2AR regulation by an intracellular positive allosteric modulator.Science, 364 (6447):1283-1287.

6.     Xiangyu Liu^#*,Xinyu Xu^#, Daniel Hilger^#, Philipp Aschauer, Johanna K.S. Tiemann, Yang Du, Hongtao Liu, Kunio Hirata, Xiaoou Sun, Ramon Guixà-González, Jesper M. Mathiesen, Peter W. Hildebrand, Brian Kobilka*.(2019) Structural insights into the process of GPCR-G protein complex formation.Cell,177(5):1243-1251.

7.     Hongtao Liu^#, Josefa Hofmann^#, Inbar Fish^#, Benjamin Schaake, Katrin Eitel, Amelie Bartuschat, Jonas Kaindl, Hannelore Rampp, Ashutosh Banerjee, Harald Hübner, Mary J. Clark, Sandra G. Vincent , John T. Fisher, Markus R. Heinrich, Kunio Hirata, Xiangyu Liu*, Roger K. Sunahara, Brian K. Shoichet*, Brian K. Kobilka*, Peter Gmeiner*. (2018)Structure-guided development of selective muscarinic M3 acetylcholine receptor antagonists.PNAS.,115(47):12046-12050.

8.     Xiangyu Liu^#,Seungkirl Ahn^#, Alem W. Kahsai, Kai-Cheng Meng, Naomi R. Latorraca, Biswaranjan Pani, A. J. Venkatakrishnan, Ali Masoudi, William I. Weis, Ron O. Dror, Xin Chen, Robert J. Lefkowitz*, Brian K. Kobilka*. (2017) Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure. Nature, 548:480-484.

9.     Yi-He Huang^#, Xiang-Yu Liu^#, Xiao-Xia Du, Zheng-Fan Jiang, Xiao-Dong Su. (2012) The Structural Basis for the Sensing and Binding of Cyclic di-GMP by STING. Nature Structural & Molecular Biology,19: 728–730.

10. Pontus Gourdon^#, Xiang-Yu Liu^#, Tina Skjørringe, J. Preben Morth, Lisbeth Birk Møller*, Bjørn Panyella Pedersen, Poul Nissen*. (2011)Crystal structure of a copper-transporting PIB-type ATPase. Nature, 475: 59-64.