Liu Zhi-Jie group current research is focused on the study of human G protein coupled receptors (GPCR) and related cell signal transductions. GPCRs constitute the largest protein family in human body, they are responsible for about 80% of the cell surface signal transductions, play important roles in many physiological activities and related to many diseases. More than 30% of marketed drugs target GPCRs. However, GPCRs are only responsible for the initial step of cell surface signal transductions, there are more than 200 downstream signaling pathways participated in the cell functional modulations which we know very little about. The long term research focus will be shifted from GPCR structural biology to GPCR mediated signaling transduction mechanism in neuron cells by integrating different imaging and functional analysis methods. Our special interest is GPCR biased signaling which is important for developing effective and side effect free drugs.
Zhi-Jie Liu, Professor, Executive Director
Current Lab Members
International teams of scientists take important step towards deciphering a new paradigm in drug discovery1 Feb, 2018
February 1, 2018 - Polypharmacology is the next generation of disease treatment promising more effective drugs that are less toxic and have fewer side effects. However, polypharmacological drugs, which simultaneously act on multiple targets, remain extremely difficult to develop, though maybe not for long according to a study published this week in Cell....Read more
Congratulations to Professor Zhi-Jie Liu being appointment for the first tenure professor of ShanghaiTech University31 Jan, 2018
January 31, 2018 - ShanghaiTech University (STU) held “tenure professor appointment”, “excellent teachers” and “outstanding staff”awards ceremony. All the STU leaderships, faculty and staffs attended the big event. Most important, it was the first tenure professor appointment at STU. The ceremonywas chaired by provost and vice-president Yin Jie and vice president Renchang Hua....Read more
July 6, 2017 — A team of scientists led by Professor Zhi-jie Liu at the iHuman Institute of ShanghaiTech University has determined the 3-dimensional molecular structure of the agonist-bound human cannabinoid receptor CB1. The work reveals the structural features of agonist-bound CB1 and the activation mechanism of the receptor. The results, described in a paper entitled “Crystal structures of agonist-bound human cannabinoid receptor CB1”, published online on July 6, 2017 in the prestigious journal Nature....Read more
Key Diabetes Receptor Structure Determined by International Collaboration—Shanghai Led Consortium Produces High Resolution 3D map of GLP-1R17 May, 2017
May 17, 2017 — An international team led by the iHuman Institute, ShanghaiTech University has determined the 3-dimensional molecular structure of the human glucagon-like peptide-1 receptor (GLP-1R) drug binding domain. The work reveals molecular mechanisms of allosteric regulation in class B G protein-coupled receptors (GPCRs). The results, described in a paper entitled “Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators”, is published online on May 17, 2017 in the journal Nature. This paper is published simultaneously with a companion paper led by colleagues at the Shanghai Institute of Materia Medica (SIMM) describing the full-length glucagon receptor in the same journal....Read more
iHuman Institute Scientific Research Selected as Shanghai Top Ten Science & Technology Stories for 20169 Jan, 2017
January 9, 2017 – The Shanghai city government recently announced the 2016 Shanghai Top Ten Science & Technology stories. Included in the list is the structure of cannabinoid receptor 1 (CB1), also known as the “marijuana receptor” published in the prestigious international journal Cell in October, 2016....Read more
1. Peng, Y., J. D. McCorvy, K. Harpsoe, K. Lansu, S. Yuan, P. Popov, L. Qu, M. Pu, T. Che, L. F. Nikolajsen, X. P. Huang, Y. Wu, L. Shen, W. E. Bjorn-Yoshimoto, K. Ding, D. Wacker, G. W. Han, J. Cheng, V. Katritch, A. A. Jensen, M. A. Hanson, S. Zhao, D. E. Gloriam, B. L. Roth, R. C. Stevens and Z. J. Liu (2018). 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology. Cell, 172(4), 719-730.
2. T. Hua, K. Vemuri, S. Nikas, R. Laprairie, Y. Wu, L. Qu, M. Pu, A. Korde, S. Jiang, J.H. Ho, GW. Han, D. Ding, X. Li, H. Liu, S. M. Hanson, S. Zhao*, L. Bohn*, A. Makriyannis*, R Stevens. Liu ZJ* (2017) Crystal Structure of agonist-bound Human Cannabinoid Receptor CB1. Nature, 547 (7664): 468-471.
3. Song G, Yang D, Wang Y, Graaf C.D, Zhou Q, Jiang S, Liu K, Cai X, Dai A, Lin G, Liu D, Wu F, Wu Y, Zhao S, Ye L, Han G.W, Lau J, Wu B, Hanson M.A, Liu Z.J*, Wang M.W*, and Steven R.C* (2017) Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators, Nature, 546(7657):312-315.
4. T. Hua, K. Vemuri, M. Pu, L. Qu, GW. Han, Y. Wu, S. Zhao, W. Shui, S. Li, A. Korde, R. Laprairie, E. Stahl, J. Ho, N. Zvonok, H. Zhou, I. Kurareva, B. Wu, Q. Zhao, M. Hanson, L. Bohn*, A. Makriyannis*, R Stevens*. ZJ. Liu* (2016) Crystal Structure of the Human Cannabinoid Receptor CB1. Cell, 167(3):750-762.
5. Liu B, Ouyang S, Makarova K, Xia Q, Zhu Y, Li Z, Guo L, Koonin E, Liu ZJ*, Huang L*. (2015) A primase subunit essential for efficient primer synthesis by an archaeal eukaryal-type primase. Nat Commun. 6:7300.
6. J. Gu, Y. Feng, X. Feng, C. Sun, L. Lei, W. Ding, F. Niu, L. Jiao, M. Yang, Y. Li, X. Liu, J. Song, Z. Cui, D. Han, C. Du, Y. Yang, S. Ouyang*, Z. J. Liu*, W. Han*, (2014) Structural and Biochemical Characterization Reveals LysGH15 as an Unprecedented "EF-Hand-Like" Calcium-Binding Phage Lysin, PLOS Pathogens, 10(5) e1004109.
7. Zhao, L., Hua, t., Crowley, C., Ru, H., Ni, X., Shaw, N., Jiao, L., Ding, W., Qu, L., Hung, L., Huang, W., Liu, L., Ye, K., OuYang, S*, Cheng, G*, and Liu, Z. J*, (2014) Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage, Cell Res, 24(3):344-58
8. Niu, F., Shaw, N., Wang, Y., Jiao, L., Ding, W., Li, X., Zhu, P., Upur, H., OuYang, S*, Cheng, G*, and Liu, Z. J*, (2013) Structure of the Leanyer Orthobunyavirus Nucleoprotein-RNA complex reveals novel architecture for RNA encapsidation, PNAS, 110(22):9054-9.
9. Ru, H., Ni, X. , Zhao, L. , Crowley, C., Ding, W., Hung, L., Shaw, N., Cheng, G*. and Liu, Z. J*, (2013) Structural basis for termination of AIM2-mediated signaling by p202. Cell Res, 23(6):855-8.
10. OuYang, S, Song, X, Wang, Y, Ru, H., Shaw, N., Jiang, Y., Niu, F., Zhu, Y., Qiu, W., Parvatiyar, K., Li, Y., Zhang, R., Cheng, G*., and Liu, Z. J*, (2012) Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding, Immunity, 36(6): 1073-1086.
11. Liu, Z. J*, Chen, L., Wu, D., Ding, W., Zhang H., Zhou, W., Fu, Z. & Wang, BC*, (2011) A multi-dataset data-collection strategy produces better diffraction data. Acta Cryst A67, 544-549.
12. Wu, D., Li, Y., Song, GJ, Zhang, R., Joachimiak, A., Shaw, N., & Liu, Z. J*. (2009) Structural basis for the inhibition of human MTHFS by N10-substituted folate analogues. Cancer Research, 69(18), 7294-301. (Cover)
13. Shaw, N., Zhao, M., Cheng, C., Xu, H., Saarikettu, J., Li, Y., Da, Y., Yao, Z., Silvennoinen, O., Yang, J.*, Liu, Z. J*., Wang, B. C. & Rao, Z. (2007) The multifunctional human p100 protein 'hooks' methylated ligands. Nat Struct Mol Biol, 14(8), 779-84.
14. Shaw, N., Cheng, C., and Liu, Z. J*, (2007) Procedure for reductive methylation of protein to improve crystallizability. Nature Protocols DOI: 10.1038/nprot.2007.287
15. Liu, Z.J., Vysotski, E.S., Chen, C.J., Rose, J.P., Lee, J., and Wang, B.C.* (2000). Structure of the Ca2+-regulated photoprotein obelin at 1.7 A resolution determined directly from its sulfur substructure, Protein Sci 9, 2085-2093.
16. Liu, Z.J., Sun, Y.J., Rose, J., Chung, Y.J., Hsiao, C.D., Chang, W.R., Kuo, I., Perozich, J., Lindahl, R., Hempel, J., and Wang, B.C.* (1997). The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold. Nat Struct Biol, 4, 317-326.
17. Liu, Z.J., and Liang, D.C.* (1995). A Preliminary study on the determination of integral radius in molecular replacement method. Acta Biophysica Sinica, 11, 139-143.
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