General

LI, Dianfan

Ph.D., Principle Investigator

National Center for Protein Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 333 Haike Road, Pudong, Shanghai, China.

Tel: +86 21 2077 8212

Email: dianfan.li@@sibcb.ac.cn

Research Areas

Research Interest:

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. 

Publications

1          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 8, 1691(2017).

2          Zha, J. & Li, D*. Lipid cubic phase for membrane protein X-ray crystallography. in Membrane Biophysics Ch. 7, (Springer, 2017).

3          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).

4          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).

5          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).

6          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).

7          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).

8          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).

9          Li, D., Stansfeld, P. J., Sansom, M. S. P., Keogh, A., Vogeley, L., Howe, N., Lyons, J. A., Aragao, D., Fromme, P., Fromme, R., Basu, S., Grotjohann, I., Kupitz, C., Rendek, K., Weierstall, U., Zatsepin, N. A., Cherezov, V., Liu, W., Bandaru, S., English, N. J., Gati, C., Barty, A., Yefanov, O., Chapman, H. N., Diederichs, K., Messerschmidt, M., Boutet, S., Williams, G. J., Marvin Seibert, M. & Caffrey, M*. Ternary structure reveals mechanism of a membrane diacylglycerol kinase.  6, 10140, (2015).

10        Li, D., Pye, V. E. & Caffrey, M*. Experimental phasing for structure determination using membrane-protein crystals grown by the lipid cubic phase method. Acta Crystallogr D 71, 104-122, (2015).

11        Kang, Y., Zhou, X. E., Gao, X., He, Y., Liu, W., Ishchenko, A., Barty, A., White, T. A., Yefanov, O., Han, G. W., Xu, Q., de Waal, P. W., Ke, J., Eileen Tan, M. H., Zhang, C., Moeller, A., West, G. M., Pascal, B., Van Eps, N., Caro, L. N., Vishnivetskiy, S. A., Lee, R. J., Suino-Powell, K. M., Gu, X., Pal, K., Ma, J., Zhi, X., Boutet, S., Williams, G. J., Messerschmidt, M., Gati, C., Zatsepin, N. A., Wang, D., James, D., Basu, S., Roy-Chowdhury, S., Conrad, C., Coe, J., Liu, H., Lisova, S., Kupitz, C., Grotjohann, I., Fromme, R., Jiang, Y., Tan, M., Yang, H., Li, J., Wang, M., Zheng, Z., Li, D., Howe, N., Zhao, Y., Standfuss, J., Diederichs, K., Dong, Y., Potter, C. S., Carragher, B., Caffrey, M., Jiang, H., Chapman, H. N., Spence, J. C. H., Fromme, P., Weierstall, U., Ernst, O. P., Katritch, V., Gurevich, V. V., Griffin, P. R., Hubbell, W. L., Stevens, R. C., Cherezov, V., Melcher, K. & Xu, H. E*. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561-567, (2015).

12        Weinert, T., Olieric, V., Waltersperger, S., Panepucci, E., Chen, L., Zhang, H., Zhou, D., Rose, J., Ebihara, A., Kuramitsu, S., Li, D., Howe, N., Schnapp, G., Pautsch, A., Bargsten, K., Prota, A. E., Surana, P., Kottur, J., Nair, D. T., Basilico, F., Cecatiello, V., Pasqualato, S., Boland, A., Weichenrieder, O., Wang, B. C., Steinmetz, M. O., Caffrey, M. & Wang, M*. Fast native-SAD phasing for routine macromolecular structure determination. Nat Methods 12, 131-133, (2014).

13       Weierstall, U*., James, D., Wang, C., White, T. A., Wang, D., Liu, W., Spence, J. C., Bruce Doak, R., Nelson, G., Fromme, P., Fromme, R., Grotjohann, I., Kupitz, C., Zatsepin, N. A., Liu, H., Basu, S., Wacker, D., Han, G. W., Katritch, V., Boutet, S., Messerschmidt, M., Williams, G. J., Koglin, J. E., Marvin Seibert, M., Klinker, M., Gati, C., Shoeman, R. L., Barty, A., Chapman, H. N., Kirian, R. A., Beyerlein, K. R., Stevens, R. C., Li, D., Shah, S. T., Howe, N., Caffrey, M. & Cherezov, V*. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5, 3309, (2014).

14        Tan, J#., Rouse, S. L#., Li, D#., Pye, V. E., Vogeley, L., Brinth, A. R., El Arnaout, T., Whitney, J. C., Howell, P. L., Sansom, M. S. & Caffrey, M*. A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr D 70, 2054-2068, (2014).

15        Nji, E., Li, D., Doyle, D. A. & Caffrey, M*. Cloning, expression, purification, crystallization and preliminary X-ray diffraction of a lysine-specific permease from Pseudomonas aeruginosa. Acta Crystallogr F 70, 1362-1367, (2014).

16        Lyons, J. A#., Parker, J. L#., Solcan, N., Brinth, A., Li, D., Shah, S. T., Caffrey, M*. & Newstead, S*. Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters. EMBO Rep 15, 886-893, (2014).

17        Li, D., Howe, N., Dukkipati, A., Shah, S. T., Bax, B. D., Edge, C., Bridges, A., Hardwicke, P., Singh, O. M., Giblin, G., Pautsch, A., Pfau, R., Schnapp, G., Wang, M., Olieric, V. & Caffrey, M*. Crystallizing Membrane Proteins in the Lipidic Mesophase. Experience with Human Prostaglandin E2 Synthase 1 and an Evolving Strategy. Cryst Growth Des 14, 2034-2047, (2014).

18        Li, D. & Caffrey, M*. Renaturing membrane proteins in the lipid cubic phase, a nanoporous membrane mimetic. Sci Rep 4, 5806, (2014).

19        Caffrey, M*., Li, D., Howe, N. & Shah, S. T. 'Hit and run' serial femtosecond crystallography of a membrane kinase in the lipid cubic phase. Philos Trans R Soc Lond B Biol Sci 369, 20130621, (2014).

20        Caffrey, M*., Eifert, R., Li, D. & Howe, N. The lipid cubic phase or method for crystallizing proteins. Bushings for better manual dispensing. J Appl Crystallogr 47, 1804-1806, (2014).

21        Boland, C#., Li, D#., Shah, S. T., Haberstock, S., Dotsch, V., Bernhard, F. & Caffrey, M*. Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination. Cell Mol Life Sci 71, 4895-4910, (2014).

22        Liu, W., Wacker, D., Gati, C., Han, G. W., James, D., Wang, D., Nelson, G., Weierstall, U., Katritch, V., Barty, A., Zatsepin, N. A., Li, D., Messerschmidt, M., Boutet, S., Williams, G. J., Koglin, J. E., Seibert, M. M., Wang, C., Shah, S. T., Basu, S., Fromme, R., Kupitz, C., Rendek, K. N., Grotjohann, I., Fromme, P., Kirian, R. A., Beyerlein, K. R., White, T. A., Chapman, H. N., Caffrey, M., Spence, J. C., Stevens, R. C. & Cherezov, V*. Serial femtosecond crystallography of G protein-coupled receptors. Science 342, 1521-1524, (2013).

23        Li, D., Shah, S. T. A. & Caffrey, M*. Host Lipid and Temperature as Important Screening Variables for Crystallizing Integral Membrane Proteins in Lipidic Mesophases. Trials with Diacylglycerol Kinase. Cryst Growth Des 13, 2846-2857, (2013).

24        Li, D., Lyons, J. A., Pye, V. E., Vogeley, L., Aragao, D., Kenyon, C. P., Shah, S. T., Doherty, C., Aherne, M. & Caffrey, M*. Crystal structure of the integral membrane diacylglycerol kinase. Nature 497, 521-524, (2013).

25        Hopper, J. T., Yu, Y. T., Li, D., Raymond, A., Bostock, M., Liko, I., Mikhailov, V., Laganowsky, A., Benesch, J. L., Caffrey, M., Nietlispach, D. & Robinson, C. V*. Detergent-free mass spectrometry of membrane protein complexes. Nat Methods 10, 1206-1208, (2013).

26        Li, D., Boland, C., Walsh, K. & Caffrey, M*. Use of a robot for high-throughput crystallization of membrane proteins in lipidic mesophases. J Vis Exp, e4000, (2012).

27        Li, D., Boland, C., Aragao, D., Walsh, K. & Caffrey, M*. Harvesting and cryo-cooling crystals of membrane proteins grown in lipidic mesophases for structure determination by macromolecular crystallography. J Vis Exp, e4001, (2012).

28        Nederlof, I., Hosseini, R., Georgieva, D., Luo, J., Li, D. & Abrahams, J. P*. A Straightforward and Robust Method for Introducing Human Hair as a Nucleant into High Throughput Crystallization Trials. Cryst Growth Des 11, 1170-1176, (2011).

29        Li, D., Lee, J. & Caffrey, M*. Crystallizing Membrane Proteins in Lipidic Mesophases. A Host Lipid Screen. Cryst Growth Des 11, 530-537, (2011).

30        Li, D. & Caffrey, M*. Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes. Proc Natl Acad Sci U S A 108, 8639-8644, (2011).


Students

现指导学生

姚贺帮  01  19183  

蔡洪敏  01  19183  

查嘉璐   02  19181  

汤艳楠  01  19183  

李婷婷  01  19183  

李艳芳  02  63228