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院士风采
杰出青年
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全所PI名录 >

 
李典范
研究员,研究组长,博士生导师
E-mail: dianfan.li@@sibcb.ac.cn


个人简介

1999与2002年于湖南农业大学分别获学士与硕士学位。2006年获武汉大学博士学位。2006年至2014年先后在爱尔兰利默里克大学与都柏林圣三一学院从事博士后研究。2014年10月回国工作,现任中科院上海生命科学院生化与细胞所,国家蛋白质科学中心研究员,课题组长,博士生导师。2015年上海市“浦江人才计划A类”资助。


研究方向

膜蛋白结构与功能及前沿技术


研究工作

在脂质代谢酶等膜蛋白结构功能研究方面,解析甘油二酯激酶结构并揭示功能机制;解析炎症、癌症药物靶标前列腺素E2合成酶结构并揭示活性中心组装机制;解析病原菌中与抗药性相关的绿脓杆菌类多糖转运蛋白结构;解析磷脂合成中甘油三磷酸脂酰转移酶的高分辨率结构,揭示其与已有7次跨膜结构不同的拓扑组装,以及一个全新的“底物助催化”的酰基转移酶学机制。

在发展与膜蛋白结构研究紧密关联的脂立方相LCP技术体系研究方面,提出并成熟LCP微晶优化策略和构建LCP重原子标记法;利用LCP的类天然脂双分子层结构高效复性膜蛋白甘油二酯激酶并解析复性后蛋白的晶体结构;揭示纯化跨膜酶二酰基甘油激酶、磷脂酰甘油磷酸合成酶和甘油三磷酸脂酰转移酶在LCP体系中的酶学机制;利用自由电子激光前沿技术对LCP生长的膜蛋白微晶进行结构解析。


代表性论文

  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

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