Deputy Director, NCPSS Deputy Chief Engineer, NFPSS
Our laboratory studies the structure and function of the proteins related to important biological processes or human diseases. Our technical advantage is synchrotron radiation x-ray source, based on which we will develop new technologies and methods for structural biology.
1. Metastatic Factors
Cancer is an inherent disease with severe threat to public health, which is rapidly expanding in China. According to WHO, most of cancer patients die of metastasis, instead of original cancer. Therefore, preventing cancer cells from metastasis is an essential basis of thoroughly curing cancer. Metastasis is a kind of cell migration, but in an abnormal way. Cell adhesion molecules, including integrins, play a key role in the process of cell migration. To fulfill the function of integrin, it has to be activated by a number of intracellular activator proteins. In metastatic cells, some integrin activators were observed to yield a high level of expression, remarkably different from normal cells. Those factors are hence called metastatic factors. However, the mechanism of this activation process and the subsequent conformational changes are still unclear. We believe that our structural biology research will bring an in-depth understanding of the activation process of integrin by metastatic factors, as well as the related processes of cell adhesion and cell migration, providing novel ideas for cancer therapies aiming metastasis.
2. Neurodegeneration diseases
Neurodegeneration diseases are a group of diseases involving the progressive loss of structure or function of patients’ neurons, including Alzheimer’s, amyotrophic lateral sclerosis (ALS), etc. With the molecular progress of biological research, the abnormal protein molecules related to various neurodegeneration diseases have been identified. Through the structural biology studies of those proteins, the pathological understanding of neurodegeneration will be more direct and accurate. For instance, the expression products of the newly discovered genes in ALS research have inheritable mutations. Those genes exhibit multi-functionalities, but the exact mechanism remains unknown. It is possible for structural biology research to promote our understanding of the pathological mechanisms of neurodegeneration diseases such as ALS.
1. Song, X., Yang, J, Hirbawi, J., Ye, S., Perera, H. D., Goksoy, E., Dwivedi, P., Plow, E.F., Zhang, RG*., and Qin, J*. A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion. Cell Research. doi: 10.1038/cr.2012.97. (Epub ahead of print)
2. Liu, Y., Zhu, Y., Ye, S., and Zhang, RG. Crystal structure of kindlin-2 PH domain reveals a conformational transition for its membrane anchoring and regulation of integrin activation. Protein & Cell, 2012, 3:434-440.
3. 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, Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding, Immunity, 2012, 36(6): 1073-1086.
4. Kim Y, Joachimiak G, Ye Z, Binkowski TA, Zhang RG, Gornicki P, Callahan SM, Hess WR, Haselkorn R, Joachimiak A. Structure of transcription factor HetR required for heterocyst differentiation in cyanobacteria. Proc Natl Acad Sci U S A. 2011, 108:10109-14.
5. Pardee KI, Xu X, Reinking J, Schuetz A, Dong A, Liu S, Zhang RG, Tiefenbach J, Lajoie G, Plotnikov AN, Botchkarev A, Krause HM, Edwards A. The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta. PLoS Biol. 2009, 7:e43.
6. X He, J Zhou, M Bartlam, RG Zhang, J Ma, Z Lou, X Li, J Li, A Joachimiak, Z Zeng, R Ge, Z Rao & Y Liu. Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus. Nature, 2008, 454(7208): 1123-1126
7. VV Lunin, E Dobrovetsky, G Khutoreskaya, RG Zhang, A Joachimiak, DA Doyle, A Bochkarev, ME Maguire, AM Edwards & CM Koth. Crystal structure of the CorA Mg2+ transporter. Nature, 2006, 440 (7085): 833-837
8. M Shimaoka, T Xiao, JH Liu, YT Yang, YC Dong, CD Jun, A McCormack, RG Zhang, A Joachimiak, J Takagi, JH Wang & T Springer. Structures of the α LI domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell, 2003, 112: 99-111
9. JP Xiong, S Thilo, RG Zhang, A Joachimiak, SL Goodman & MA Arnaout. Crystal structure of integrin aVb3 in complex with an Arg-Gly-Asp ligand. Science, 2002, 296: 151-155
10. RG Zhang, T Pappas, J Brace, P Miller, T Oulmassov, J Molyneaux, J Anderson, J Bashkin, S Winans & A Joachimiak. Structure of a bacterial Quorum-Sensing Transcription factor Complexed with Pheromone and DNA. Nature, 2002, 417: 971-974
11. Xiong JP, Stehle T, Diefenbach B, Zhang RG, Dunker R, Scott DL, Joachimiak A, Goodman SL, Arnaout MA. Crystal structure of the extracellular segment of integrin alpha Vbeta3. Science. 2001, 294:339-45.
12. Z Otwinowski, RW Schevitz, RG Zhang, CL Lawson, RQ Marmorstein, A Joachimiak, B Luisi, & PB Sigler. Crystal structure of the Trp operator/repressor complex at atomic resolution. Nature, 1988, 335: 321-329
13. RG Zhang, A Joachimiak, CL Lawson, RW Schevitz, Z Otwinowski & PB Sigler. The crystal structure of the Trp aporepressor at 1.8 Å, showing how tryptophan enhances DNA affinity. Nature, 1987, 327: 591-597