Xu Fei Professor
Degree :PhD Affiliation : Position : Assistant Director Honor : Final education : Graduate School : Tel : Fax : Office : Add : Email :xufei@shanghaitech.edu.cn Research Group: Group Website: Research Area:Membrane protein structural biology

Education Background

Working Experience

Research Interests

New target identification and validation is the main driver of innovative drug discovery; the GPCR superfamily has been so-far the most successful class of drug targets, yet the many orphan receptors are regarded as undruggable targets owing to the limited understanding of their structure-function relationship. The research interests at the Xu lab center on developing multiple structural biology methods in studying structure-function relationship of important human membrane proteins and untapped drug targets. 

Research Achievement

In the past five years, we have made systematic achievements in this area and published our innovative work. For example: we reported the structures of several orphan receptors in different functional states, which for the first time elucidated the unique molecular recognition and self-activation mechanisms for the orphan GPCRs (Nature 2020Nat Commun 2023Cell Disc 2023); uncovered the first high-resolution structures of two Frizzled receptors and resolved the challenges of drug discovery toward these emerging oncology targets (Nature 2018, Cell Res 2021); deciphered the molecular mechanism for a neuronal ion channel regulated by lipids and drug molecules which is an important target for hearing loss (Neuron 2022); presented the structural evidence for the existence of dimerization for a class A GPCR and its implication in modulating cell signaling (NSMB 2022). These advancements in the research frontiers of membrane protein structural biology provided a wealth of knowledge in new drug targets and mechanisms, unlocked the visible molecular interaction for the undruggable targets, thus accelerated the translation of basic research toward new ligand screening and drug discovery. 

Representative Publications

1.       Lin Xi, Chen B, Wu Y, Han Y, Qi A, Wang J, Yang Z, Wei X, Zhao T, Wu L, Xie X, Sun J, Zheng J, Zhao S, Xu F. Cryo-EM structures of orphan GPR21 signaling complexes. Nat Commun. 2023, 14(1):216. doi: 10.1038/s41467-023-35882-w.


2.       Yue Yang, Liu L, Wu LJ, Wu Y, Wang L, Li F, Liu J, Han GW, Chen B, Lin X, Brouillette RL, Breault É, Longpré JM, Shi S, Lei H, Sarret P, Stevens RC, Hanson MA, Xu F. Structural insight into apelin receptor-G protein stoichiometry. Nat Struct Mol Biol. 2022, 29(7):688-697


3.       Chen Yuxiang, Chen B, Wu T, Zhou F, Xu F. Cryo-EM structure of human κ-opioid receptor-Gi complex bound to an endogenous agonist dynorphin A. Protein & Cell. pwac033, https://doi.org/10.1093/procel/pwac033.


4.       Zheng You, Liu H, Chen Y, Dong S, Wang F, Wang S, Li GL, Shu Y, Xu F. Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel. Neuron. 2022, 19;110(2):237-247.


5.       Xu Lu, Chen B, Schihada H, Wright SC, Turku A, Wu Y, Han GW, Kowalski-Jahn M, Kozielewicz P, Bowin CF, Zhang X, Li C, Bouvier M, Schulte G, Xu F. Cryo-EM structure of constitutively active human Frizzled 7 in complex with heterotrimeric Gs. Cell Res. 2021, 31(12):1311-1314.


6.       Lin Xi, Li M, Wang N, Wu Y, Luo Z, Guo S, Han GW, Li S, Yue Y, Wei X, Xie X, Chen Y, Zhao S, Wu J, Lei M, Xu F. Structural basis of ligand recognition and self-activation of orphan GPR52. Nature. 2020, 579(7797):152-157.


7.       Yang Shifan, Wu Y, Xu TH, de Waal PW, He Y, Pu M, Chen Y, DeBruine ZJ, Zhang B, Zaidi SA, Popov P, Guo Y, Han GW, Lu Y, Suino-Powell K, Dong S, Harikumar KG, Miller LJ, Katritch V, Xu HE, Shui W, Stevens RC, Melcher K, Zhao S, Xu F. Crystal structure of the Frizzled 4 receptor in a ligand-free state. Nature. 2018, 560(7720):666-670.


8.       Zhang Xianjun, Zhao F, Wu Y, Yang J, Han GW, Zhao S, Ishchenko A, Ye L, Lin X, Ding K, Dharmarajan V, Griffin PR, Gati C, Nelson G, Hunter MS, Hanson MA, Cherezov V, Stevens RC, Tan W, Tao H, Xu F. Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand. Nat Commun. 2017, 8:15383.


9.       Ma Yingli, Yue Y, Ma Y, Zhang Q, Zhou Q, Song Y, Shen Y, Li X, Ma X, Li C, Hanson MA, Han GW, Sickmier EA, Swaminath G, Zhao S, Stevens RC, Hu LA, Zhong W, Zhang M, Xu F. Structural Basis for Apelin Control of the Human Apelin Receptor. Structure. 2017, 6;25(6):858-866.


10.   Zhang Xianjun, Dong S, Xu F. Structural and Druggability Landscape of Frizzled G Protein-Coupled Receptors. Trends Biochem Sci. 2018, 43(12): 1033-1046.


11.   Zhang Xianjun, Stevens R. C, Xu F. The importance of ligands for G protein-coupled receptor stability. Trends Biochem Sci, 2015, 40(2): 79-87.





Group Member

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