Home CAS Center for Excellence


Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
LI Dianfan
Ph.D., Professor
National Center for Protein Sciences (Shanghai), Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, 333 Haike Road, Pudong, Shanghai, China.
Email: dianfan.li@@sibcb.ac.cn

Research Areas
Protein Sciences; Membrane Protein Structure Biology

Research Interests

Membrane proteins, including transporters, channels, receptors, and lipid metabolizing enzymes, play vital roles in biology, and makes up 60% of approved drug targets. Revealing their three dimension structures is crucial in understanding how these important macromolecules function at the molecule level. One research direction in our lab is to solve structures of physiologically and pharmaceutically important membrane proteins, mainly by X-ray crystallography. Getting diffraction-quality crystal a key step in this approach. The lipid cubic phase, where the membrane proteins are hosted in native-like bilayers made of lipids, mostly monoacylglycerol with a single cis-double bond in the fatty chain, is the main method we  use and develop for crystalizing and characterizing membrane proteins.

Selected Publications

  1. Li, Z#., Tang, Y#. & Li, D*. In Meso Crystallization of the Integral Membrane Glycerol 3-phosphate Acyltransferase with Substrates. Cryst Growth Des 2018 DOI: 10.1021/acs.cgd.7b01678
  2. Li, Z#., Tang, Y#., Wu, Y., Zhao S., Bao, J., Luo, Y. & Li, D*. Structural insights into the committed step of bacterial phospholipid biosynthesis. Nat Commun 2017 8:1691.
  3. Zha, J. & Li, D*. Lipid cubic phase for membrane protein X-ray crystallography. in Membrane Biophysics Ch. 7, (Springer, in press).
  4. D Li, JA Lyons, VE Pye, L Vogeley, D Aragao, C Kenyon, ST Shah, C Doherty, M Aherne, M Caffrey. Crystal structure of the integral membrane diacylglycerol kinase. Nature 2013 497:521-4.
  5. D Li, P. J. Stansfeld, M. S. P. Sansom, A. Keogh, L. Vogeley, N. Howe, J. A. Lyons, D. Aragao, P. Fromme, R. Fromme, S. Basu, I. Grotjohann, C. Kupitz, K. Rendek, U. Weierstall, N. A. Zatsepin, V. Cherezov, W. Liu, S. Bandaru, N. J. English, C. Gati1, A. Barty, O. Yefanov, H. Chapman, K. Diederichs, M. Messerschmidt S. Boutet, G. J. Williams, M. M. Seibert, M. Caffrey. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nat Commun. 2015 6:10140
  6. D Li, M Caffrey. Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes.Proc. Natl. Acad. Sci. USA 2011 108:8639-44.
  7. D Li, VE Pye, M Caffrey. Experimental phasing for structure determination using membrane protein crystals grown by the lipid cubic phase method. Acta Crystallogr. D. 2015 71:104-22
  8. D Li, M Caffrey. Renaturing Membrane Proteins in the Lipid Cubic Phase, a Nanoporous Membrane Mimetic. Sci. Rep. 2014 4:5806
  9. D Li, N Howe, A Dukkipati, STA Shah, BD Bax, C Edge, A Bridges, P Hardwick, OMP Singh, A Pautsch, R Pfau, G Schnapp, M Wang, V Olieric, M Caffrey. Crystallizing membrane proteins in the lipidic mesophase. Experience with human prostaglandin E2 synthase 1 and an evolving strategy. Cryst. Growth Des. 2014 14:2037-2047
  10. D Li, ST Shah, M Caffrey. Host lipid and temperature as important screening variables for crystallizing integral membrane proteins in lipidic mesophases. Trials with diacylglycerol kinase. Cryst. Growth Des. 2013 13:2846-57.
  11. D Li, J Lee, M Caffrey. Crystallizing membrane proteins in lipidic mesophases. A host lipid screen. Cryst. Growth Des. 2011 11:530-7.
  12. C Boland, D Li* (co-first author), STA Shah, S Haberstock, V Dötsch, F Bernhard, M Caffrey. Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination. Cell. Mol. Life Sci. 2014 71:4895-4910
  13. J Tan*, SL Rouse*, D Li* (co-first author), VE Pye, L Vogeley, A Brinth, T El Arnaout, JC Whitney, PL Howell, MSP Sansom, M Caffrey. A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr. D. 2014. 70:2054-2068.
  14. Y Kang, X. E. Zhou, X. Gao, Y. He, W. Liu, A Ishchenko, A Barty, T. A. White, O. Yefanov, G. W. Han, Q. Xu, P. W. de Waa, J. Ke, M. H. Tan, C. Zhang, A. Moeller, G. M. West, B. D. Pascal, N. Van Eps, L. N. Caro, S. A. Vishnivetskiy, R. J. Lee, K. M. Suino-Powell, X. Gu, K. Pal, J. Ma, X. Zhi, S. Boutet, G. J. Williams, M. Messerschmidt, C. Gati, N. A. Zatsepin, D. Wang, D. James, S. Basu, S. Roy-Chowdhury, C. E. Conrad, J. Coe, H. Liu, S. Lisova, C. Kupitz, I. Grotjohann, R. Fromme, Y. Jiang, M. Tan, H. Yang, J. Li, M. Wang, Z. Zheng, D. Li, N. Howe, Y. Zhao, J. Standfuss, K. Diederichs, Y. Dong, C. S. Potter, B. Carragher, M. Caffrey, H. Jiang, H. N. Chapman, J. C. Spence, P. Fromme, U. Weierstall, O. P. Ernst, V. Katritch, V. V. Gurevich, P. R. Griffin, W. L. Hubbell, R. C. Stevens, V. Cherezov, K. Melcher, H. E. Xu. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 2015 523:561-7
  15. W Liu, D Wacker, C Gati, GW Han, D James, D Wang, G Nelson, U Weierstall, V Katritch, A Barty, NA Zatsepin, D Li, M Messerschmidt, S Boutet, GJ Williams, JE Koglin, MM Seibert, C Wang, ST Shah, S Basu, R Fromme, C Kupitz, KN Rendek, I Grotjohann, P Fromme, RA Kirian, KR Beyerlein, TA White, HN Chapman, M Caffrey, JC Spence, RC Stevens, V Cherezov. Serial femtosecond crystallography of G protein-coupled receptors. Science 2013 342:1521-4
  16. T Weinert, V Olieric, S Waltersperger, E Panepucci, L Chen, H Zhang, D Zhou, J Rose, A Ebihara, S Kuramitsu, D Li, N Howe, G Schnapp, A Pautsch, K Bargsten, AE Prota, P Surana, J Kottur, DT Nair, F Basilico, V Cecatiello, S Pasqualato, A Boland, O Weichenrieder, B Wang, MO Steinmetz, M Caffrey, M Wang. Fast native-SAD phasing for routine macromolecular structure determination. Nat. Methods. 2015 12 : 131-3
  17. JT Hopper, YT Yu, D Li, A Raymond, M Bostock, I Liko, V Mikhailov, A Laganowsky, JL Benesch, M Caffrey, D Nietlispach, CV Robinson. Detergent-free mass spectrometry of membrane protein complexes. Nat. Methods 2013 10: 1206-8
  18. U Weierstall, D James, D Wang, W Liu, JCH Spence, RB Doak, G Nelson, P Fromme, R Fromme, I Grotjohann, C Kupitz, NA Zatsepin, S Basu, D Wacker, C Wang, S Boutet, M Messerschmidt, GJ Williams, JE Koglin, MM Seibert, C Gati, RL Shoeman, A Barty, HN Chapman, RA Kirian, KR Beyerlein, RC Stevens, D Li, STA Shah, N Howe, M Caffrey, V Cherezov. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat. Commun. 2014. 5: 3309
  19. Luo, Q., Yang, X., Yu, S., Shi, H., Wang, K., Xiao, L., Zhu, G., Sun, C., Li, T.,Li, D., Zhang, X., Zhou, M. & Huang, Y*. Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG. Nat Struct Mol Biol 24, 469-474, (2017).
  20. Bao, Z., Qi, X., Hong, S., Xu, K., He, F., Zhang, M., Chen, J., Chao, D., Zhao, W., Li, D., Wang, J. & Zhang, P*. Structure and mechanism of a group-I cobalt energy coupling factor transporter. Cell Res 27, 675-687, (2017).
  21. JA Lyons, JL Parker, N Solcan, A Brinth, D Li, S.T.A. Shah, M Caffrey, S Newstead. Structural basis for polyspecificity in the POT family of proton coupled oligopeptide transporters. EMBO Rep. 2014 15:886-93
  22. Zhou, X. E., Gao, X., Barty, A., Kang, Y., He, Y., Liu, W., Ishchenko, A., White, T. A., Yefanov, O., Han, G. W., Xu, Q., de Waal, P. W., Suino-Powell, K. M., Boutet, S., Williams, G. J., Wang, M., Li, D., Caffrey, M., Chapman, H. N., Spence, J. C. H., Fromme, P., Weierstall, U., Stevens, R. C., Cherezov, V., Melcher, K. & Xu, H. E*. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex. Sci Data 3, 160021, (2016).
  23. Prabhu, A., Luu, W., Li, D., Sharpe, L. & J. Brown, A*. DHCR7: A vital enzyme switch between cholesterol and vitamin D production. Prog Lipid Res 64, 138-151, (2016).
  24. Olieric, V., Weinert, T., Finke, A. D., Anders, C., Li, D., Olieric, N., Borca, C. N., Steinmetz, M. O., Caffrey, M., Jinek, M. & Wang*, M. Data-collection strategy for challenging native SAD phasing. Acta Crystallogr D 72, 421-429, (2016).
  25. Howe, V., Sharpe, L. J., Alexopoulos, S. J., Kunze, S. V., Chua, N. K., Li, D. & Brown, A. J*. Cholesterol homeostasis: How do cells sense sterol excess? Chem Phys Lipids 199, 170-178, (2016).
  26. M Caffrey, D Li, N Howe, STA Shah. ¨Hit and run¨ serial femtosecond crystallography of a membrane kinase in the lipid cubic phase. Phil. Trans. R. Soc. B. 2014. 369:20130621
  27. M Caffrey, D Li, A Dukkipati. Membrane protein structure determination using crystallography anD Lipidic mesophases: Recent advances and successes. Biochemistry 2012 51:6266-88.
  28. M Caffrey, R Eifert, D Li, N Howe. The lipid cubic phase or in meso method for crystallizing proteins. Bushings for better manual dispensing. J. Appl. Crystallogr. 2014 6:1804-1806
  29. E Nji, D Li, DA Doyle, M Caffrey. Cloning, expression, purification, crystallization and preliminary X-ray diffraction of a lysine-specific permease from Pseudomonas aeruginosa. Acta. Crystallogr. F 2014 70 : 1362-7

Education Background & Academic Experience

2014 C present Professor, National Center for Protein Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, China.
2011-2014, Research Fellow, School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
2006-2011, Postdoctoral Research Fellow, Department of Chemical and Engineer Sciences, University of Limerick, Limerick, Ireland.
2008, J1 Exchange Scholar, The Scripps Research Institute, La Jolla, CA, USA.
2002-2006, Ph.D in Molecular Biology, School of Life Sciences, Wuhan University, Wuhan, China.
1999-2002, M.Sc. in Pomology, Department of Plant Science and Technology, Hunan Agricultural University, Changsha, China.
1995-1999, B.Sc. in Horticulture, Hunan Agricultural University, Changsha, China.


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