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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,现任中科院极速快三官网(生物化学与细胞生物学研究所)研究员,课题组长,博士生导师。获中组部第11批“青年千人计划”优先资助,及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

膜蛋白参与物质转运、信号转导、能量代谢、膜脂合成等基本生命过程,在疾病发生中也起着重要作用。
 
我们实验室主要通过解析膜蛋白的三维结构来阐释其作用机制。研究重点在于脂质(磷脂与固醇)代谢相关蛋白质。我们同时发展lipid cubic phase(LCP,脂立方相)类膜环境用于膜蛋白的生化分析与结晶,及蛋白质热稳定工程技术等用于膜蛋白结构生物学研究。
 
研究成果能够丰富我们对脂质代谢过程的理解,并为开发具有代谢调控活性和具有医药应用前景的小分子化合物提供结构基础。


代表性论文

(*通讯作者; #共同第一作者) ORCID
 
  1. Yao, H#., Cai, H#. & Li, D*. Thermostabilization of membrane proteins by consensus mutation: a case study for a fungal D8-7 sterol isomerase. J Mol Biol (2020)
  2. Yuan, Y. Cao, C. Wen, M. Li, M. Dong, Y. We, L. Wu, J. Cui, T. Li, D.* Chou, J.J.* Ouyang B.* Structural Characterization of the N-Terminal Domain of the Dictyostelium discoideum Mitochondrial Calcium Uniporter. ACS Omega 10.1021/acsomega.9b04045 (2020)
  3. Li, D.*, Caffrey, M.* Structure and Functional Characterization of Membrane Integral Proteins in the Lipid Cubic Phase.  J Mol Biol  10.1016/j.jmb.2020.02.024 (2020)
  4. Cai, H#. Yao, H#. Li, T. Tang, Y. & Li, D*. High-level heterologous expression of the human transmembrane sterol Δ8,Δ7-isomerase in Pichia pastoris. Protein Expr Purif 164:105460 (2019)
  5. Tang, Y. Li, D*. Developing a High-Throughput Assay for the Integral Membrane Glycerol 3-Phosphate Acyltransferase.  Assay Drug Dev Techn 17, 267-274 (2019)
  6. Wang, D. Hu, X. Liu, C. Jia, Y. Bai, Y. Cai, C. Qang, Q. Bai, L. Yang, R. Lin, C. Liu, Y. Li, S. Qiao, F. Yao, L. Chen, L. Ge, G. Jiang, H. Li, D. Li, L. Chen, J. Shao, ZM. Zeng, YA. Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers. Cell Res 29:832-845 (2019)
  7. 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
  8. Al-Sahouri, Z., Lee, M-Y.,  Li, D., Liu, W. & Caffrey, M. The Lipid Cubic Phase as a Medium for the Growth of Membrane Protein Microcrystals: A Revolution in Structural Biology. In: Boutet S., Fromme P., Hunter M. (eds) X-ray Free Electron Lasers. Springer, Cham Ch. 4 pp 87-108 (2018)
  9. 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.
  10. Zha, J. & Li, D*. Lipid cubic phase for membrane protein X-ray crystallography. in Membrane Biophysics. Springer, Ch. 7 pp 175-220  (2018).
  11. Tang Y., Xia H., Li D*. (2018) Membrane Phospholipid Biosynthesis in Bacteria. In: Cao Y. (eds) Advances in Membrane Proteins. Springer, Singapore Ch. 4 pp 77-119 (2018)
  12. 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).
  13. 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).
  14. 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).
  15. 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).
  16. 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).
  17. 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).
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. D Li, M Caffrey. Renaturing Membrane Proteins in the Lipid Cubic Phase, a Nanoporous Membrane Mimetic. Sci. Rep. 2014 4:5806
  24. 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
  25. 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.
  26. 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
  27. 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
  28. 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
  29. 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 16:1804-1806
  30. 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
  31. 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.
  32. 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.
  33. 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
  34. 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
  35. M Caffrey, D Li, A Dukkipati. Membrane protein structure determination using crystallography and lipidic mesophases: Recent advances and successes. Biochemistry 2012 51:6266-88.
  36. 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).
  37. 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).
  38. 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. 
  39. D Li, J Lee, M Caffrey. Crystallizing membrane proteins in lipidic mesophases. A host lipid screen. Cryst. Growth Des. 2011 11:530-7. 
  40. Nederlof, I., Hosseini, R., Georgieva, D., Luo, J., D Li,. & 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).

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