基本信息

李典范 男 博导 中国科学院分子细胞科学卓越创新中心(生物化学与细胞生物学研究所)
电子邮件: dianfan.li@@sibcb.ac.cn
通信地址: 上海市浦东新区海科路333号
邮政编码: 201210
研究领域
膜蛋白结构功能及其前沿技术
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。
出版信息
发表论文
[1] Jingjing Hong, Tingting Li, Yulin Chao, Yidan Xu, Zhini Zhu, Zixuan Zhou, Weijie Gu, Qianhui Qu, Dianfan Li. Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis. NATURE COMMUNICATIONS[J]. 2024, 第 9 作者15(1): 1-17, https://doaj.org/article/57993c1664af4119a9b95d0080a2d232.[2] Xu, Yidan, Li, Tingting, Zhou, Zixuan, Hong, Jingjing, Chao, Yulin, Zhu, Zhini, Zhang, Ying, Qu, Qianhui, Li, Dianfan. Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis. NATURE COMMUNICATIONS[J]. 2023, 第 9 作者 通讯作者 14(1): http://dx.doi.org/10.1038/s41467-023-41281-y.[3] Meng, Lu, Zha, Jialu, Zhou, Bingjie, Cao, Long, Jiang, Congli, Zhu, Yuanfei, Li, Teng, Lu, Lu, Zhang, Junqi, Yang, Heng, Feng, Jian, Gu, Zhifeng, Tang, Hong, Jiang, Lubin, Li, Dianfan, Lavillette, Dimitri, Zhang, Xiaoming. A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy. PLOS PATHOGENS[J]. 2023, 第 15 作者 通讯作者 19(1): http://dx.doi.org/10.1371/journal.ppat.1011085.[4] Li, Tingting, Zhou, Bingjie, Luo, Zhipu, Lai, Yanling, Huang, Suqiong, Zhou, Yuanze, Li, Yaning, Gautam, Anupriya, Bourgeau, Salome, Wang, Shurui, Bao, Juan, Tan, Jingquan, Lavillette, Dimitri, Li, Dianfan. Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants. FRONTIERS IN MICROBIOLOGY[J]. 2022, 第 14 作者 通讯作者 13: https://doaj.org/article/388b71d2aef845efbeb6a98de15c8137.[5] Yang, Zhisen, Xia, Jing, Hong, Jingjing, Zhang, Chenxi, Wei, Hong, Ying, Wei, Sun, Chunqiao, Sun, Lianghanxiao, Mao, Yanbo, Gao, Yongxiang, Tan, Shutang, Friml, Jiri, Li, Dianfan, Liu, Xin, Sun, Linfeng. Structural insights into auxin recognition and efflux by Arabidopsis PIN1. NATURE[J]. 2022, 第 13 作者609(7927): 611-+, http://dx.doi.org/10.1038/s41586-022-05143-9.[6] Luo, Zhipu, Gu, Weijie, Wang, Yichao, Tang, Yannan, Li, Dianfan. Selenourea for Experimental Phasing of Membrane Protein Crystals Grown in Lipid Cubic Phase. CRYSTALS[J]. 2022, 第 5 作者 通讯作者 12(7): https://doaj.org/article/00e24f345aed4bddbeebbda25827e3e5.[7] Tingting Li, Bingjie Zhou, Yaning Li, Suqiong Huang, Zhipu Luo, Yuanze Zhou, Yanling Lai, Anupriya Gautam, Salome Bourgeau, Shurui Wang, Juan Bao, Jingquan Tan, Dimitri Lavillette, Dianfan Li. Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2. INTER J BIOL MACROMOL[J]. 2022, 第 14 作者 通讯作者 [8] Xu, Yidan, Jia, Guowen, Li, Tingting, Zhou, Zixuan, Luo, Yitian, Chao, Yulin, Bao, Juan, Su, Zhaoming, Qu, Qianhui, Li, Dianfan. Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins. NATURE COMMUNICATIONS[J]. 2022, 第 10 作者 通讯作者 13(1): http://apps.webofknowledge.com/CitedFullRecord.do?product=UA&colName=WOS&SID=5CCFccWmJJRAuMzNPjj&search_mode=CitedFullRecord&isickref=WOS:000795171100047.[9] Luo, Yitian, Wan, Guoyue, Zhang, Xiang, Zhou, Xuan, Wang, Qiuwen, Fan, Jialin, Cai, Hongmin, Ma, Liya, Wu, Hailong, Qu, Qianhui, Cong, Yao, Zhao, Yun, Li, Dianfan. Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae. STRUCTURE[J]. 2021, 第 13 作者 通讯作者 29(11): 1286-+, http://dx.doi.org/10.1016/j.str.2021.06.004.[10] Hebang Yao, Hongmin Cai, Tingting Li, Bingjie Zhou, Wenming Qin, Dimitri Lavillette, Dianfan Li. A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2. PLOS PATHOG[J]. 2021, 第 7 作者 通讯作者 17(3): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959386/.[11] Li, Tingting, Cai, Hongmin, Yao, Hebang, Zhou, Bingjie, Zhang, Ning, van Vlissingen, Martje Fentener, Kuiken, Thijs, Han, Wenyu, GeurtsvanKessel, Corine H, Gong, Yuhuan, Zhao, Yapei, Shen, Quan, Qin, Wenming, Tian, XiaoXu, Peng, Chao, Lai, Yanling, Wang, Yanxing, Hutter, Cedric A J, Kuo, ShuMing, Bao, Juan, Liu, Caixuan, Wang, Yifan, Richard, Audrey S, Raoul, Herve, Lan, Jiaming, Seeger, Markus A, Cong, Yao, Rockx, Barry, Wong, Gary, Bi, Yuhai, Lavillette, Dimitri, Li, Dianfan. A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection. NATURE COMMUNICATIONS[J]. 2021, 第 32 作者 通讯作者 12(1): https://doaj.org/article/e2d2ef9db7c042d5ae0d4a35e2484adb.[12] Bowei Yang, Hebang Yao, Dianfan Li, Liu, Zhenfeng. The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface. CURR RES STRUCT BIOL[J]. 2021, 第 3 作者3: 312-323, [13] Luo, Yitian, Wan, Guoyue, Zhou, Xuan, Wang, Qiuwen, Zhang, Yunbin, Bao, Juan, Cong, Yao, Zhao, Yun, Li, Dianfan. Architecture of Dispatched, a Transmembrane Protein Responsible for Hedgehog Release. FRONT MOL BIOSCI[J]. 2021, 第 9 作者 通讯作者 8: http://dx.doi.org/10.3389/fmolb.2021.701826.[14] Li, Tingting, Cai, Hongmin, Zhao, Yapei, Li, Yanfang, Lai, Yanling, Yao, Hebang, Liu, Liu Daisy, Sun, Zhou, van Vlissingen, Martje Fentener, Kuiken, Thijs, GeurtsvanKessel, Corine H, Zhang, Ning, Zhou, Bingjie, Lu, Lu, Gong, Yuhuan, Qin, Wenming, Mondal, Moumita, Duan, Bowen, Xu, Shiqi, Richard, Audrey S, Raoul, Herve, Chen, JianFeng, Xu, Chenqi, Wu, Ligang, Zhou, Haisheng, Huang, Zhong, Zhang, Xuechao, Li, Jun, Wang, Yanyan, Bi, Yuhai, Rockx, Barry, Chen, Junfang, Meng, FeiLong, Lavillette, Dimitri, Li, Dianfan. Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody. EMBO MOLECULAR MEDICINE[J]. 2021, 第 35 作者 通讯作者 13(12): https://www.doi.org/10.15252/emmm.202114544.[15] Hebang Yao, Hongmin Cai, Dianfan Li. Thermostabilization of Membrane Proteins by Consensus Mutation: A Case Study for a Fungal Δ8-7 Sterol Isomerase. JOURNAL OF MOLECULAR BIOLOGY[J]. 2020, 第 3 作者 通讯作者 432(18): 5162-5183, http://dx.doi.org/10.1016/j.jmb.2020.02.015.[16] Hongmin Cai, Hebang Yao, Tingting Li, Cedric A J Hutter, Yanfang Li, Yannan Tang, Markus A Seeger, Dianfan Li. An improved fluorescent tag and its nanobodies for membrane protein expression, stability assay, and purification. COMMUNICATIONS BIOLOGY[J]. 2020, 第 8 作者 通讯作者 3(1): http://dx.doi.org/10.1038/s42003-020-01478-z.[17] Li, Dianfan, Caffrey, Martin. Structure and Functional Characterization of Membrane Integral Proteins in the Lipid Cubic Phase. JOURNAL OF MOLECULAR BIOLOGY. 2020, 第 1 作者 通讯作者 432(18): 5104-5123, http://dx.doi.org/10.1016/j.jmb.2020.02.024.[18] Yuan, Yuan, Cao, Chan, Wen, Maorong, Li, Min, Dong, Ying, Wu, Lijie, Wu, Jian, Cui, Tanxing, Li, Dianfan, Chou, James J, OuYang, Bo. Structural Characterization of the N-Terminal Domain of the Dictyostelium discoideum Mitochondrial Calcium Uniporter. ACS OMEGA[J]. 2020, 第 9 作者 通讯作者 5(12): 6452-6460, https://doaj.org/article/f6232be39cdf4db485e6ebc55ecabe40.[19] Wang Daisong, Hu Xin, Liu Chunye, Jia Yingying, Bai Yiqin, Cai Cheguo, Wang Jingqiang, Bai Lanyue, Yang Ruikai, Lin Changdong, Liu Yirong, Li Shan, Qiao Feng, Yao Ling, Chen Li, Ge Gaoxiang, Jiang Hai, Li Dianfan, Li Lin, Chen Jianfeng, Shao Zhiming, Zeng Yi Arial. Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers. CELL RESEARCH[J]. 2019, 第 18 作者29(10): 832-845, http://sciencechina.cn/gw.jsp?action=detail.jsp&internal_id=6581802&detailType=1.[20] Hongmin Cai, Hebang Yao, Tingting Li, Yannan Tang, Dianfan Li. High-level heterologous expression of the human transmembrane sterol Δ8,Δ7-isomerase in Pichia pastoris. PROTEIN EXPRESSION AND PURIFICATION. 2019, 第 5 作者164: http://dx.doi.org/10.1016/j.pep.2019.105463.[21] Tang, Yannan, Li, Dianfan. Developing a High-Throughput Assay for the Integral Membrane Glycerol 3-Phosphate Acyltransferase. ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES[J]. 2019, 第 2 作者 通讯作者 17(6): 267-274, http://dx.doi.org/10.1089/adt.2019.935.[22] Li, Zhenjian, Tang, Yannan, Li, Dianfan. In Meso Crystallization of the Integral Membrane Glycerol 3-Phosphate Acyltransferase with Substrates. CRYSTAL GROWTH & DESIGN[J]. 2018, 第 3 作者 通讯作者 18(4): 2243-2258, http://202.127.25.143/handle/331003/3423.[23] Bao, Zhihao, Qi, Xiaofeng, Hong, Sen, Xu, Ke, He, Fangyuan, Zhang, Minhua, Chen, Jiugeng, Chao, Daiyin, Zhao, Wei, Li, Dianfan, Wang, Jiawei, Zhang, Peng. Structure and mechanism of a group-I cobalt energy coupling factor transporter. CELL RESEARCH[J]. 2017, 第 10 作者27(5): 675-687, http://dx.doi.org/10.1038/cr.2017.38.[24] Luo, Qingshan, Yang, Xu, Yu, Shan, Shi, Huigang, Wang, Kun, Xiao, Le, Zhu, Guangyu, Sun, Chuanqi, Li, Tingting, Li, Dianfan, Zhang, Xinzheng, Zhou, Min, Huang, Yihua. Structural basis for lipopolysaccharide extraction by ABC transporter LptB(2)FG. NATURE STRUCTURAL & MOLECULAR BIOLOGY[J]. 2017, 第 10 作者24(5): 469-+, http://dx.doi.org/10.1038/nsmb.3399.[25] Zhenjian Li, Yannan Tang, Yiran Wu, Suwen Zhao, Juan Bao, Yitian Luo, Dianfan Li. Structural insights into the committed step of bacterial phospholipid biosynthesis. 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ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY[J]. 2016, 第 5 作者72(Pt 3): 421-429, http://dx.doi.org/10.1107/S2059798315024110.[31] Weinert, Tobias, Olieric, Vincent, Waltersperger, Sandro, Panepucci, Ezequiel, Chen, Lirong, Zhang, Hua, Zhou, Dayong, Rose, John, Ebihara, Akio, Kuramitsu, Seiki, Li, Dianfan, Howe, Nicole, Schnapp, Gisela, Pautsch, Alexander, Bargsten, Katja, Prota, Andrea E, Surana, Parag, Kottur, Jithesh, Nair, Deepak T, Basilico, Federica, Cecatiello, Valentina, Pasqualato, Sebastiano, Boland, Andreas, Weichenrieder, Oliver, Wang, BiCheng, Steinmetz, Michel O, Caffrey, Martin, Wang, Meitian. Fast native-SAD phasing for routine macromolecular structure determination (vol 12, pg 131, 2015). NATURE METHODS. 2015, 第 11 作者12(7): 692-692, https://www.webofscience.com/wos/woscc/full-record/WOS:000357405700030.[32] Li, Dianfan, Stansfeld, Phillip J, Sansom, Mark S P, Keogh, Aaron, Vogeley, Lutz, Howe, Nicole, Lyons, Joseph A, Aragao, David, Fromme, Petra, Fromme, Raimund, Basu, Shibom, Grotjohann, Ingo, Kupitz, Christopher, Rendek, Kimberley, Weierstall, Uwe, Zatsepin, Nadia A, Cherezov, Vadim, Liu, Wei, Bandaru, Sateesh, English, Niall J, Gati, Cornelius, Barty, Anton, Yefanov, Oleksandr, Chapman, Henry N, Diederichs, Kay, Messerschmidt, Marc, Boutet, Sebastien, Williams, Garth J, Seibert, M Marvin, Caffrey, Martin. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. 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CRYSTAL GROWTH & DESIGN[J]. 2014, 第 1 作者14(4): 2034-2047, http://dx.doi.org/10.1021/cg500157x.[44] Li, Dianfan, Shah, Syed T A, Caffrey, Martin. Host Lipid and Temperature as Important Screening Variables for Crystallizing Integral Membrane Proteins in Lipidic Mesophases. Trials with Diacylglycerol Kinase. CRYSTAL GROWTH & DESIGN[J]. 2013, 第 1 作者13(7): 2846-2857, http://dx.doi.org/10.1021/cg400254v.[45] Li, Dianfan, Lyons, Joseph A, Pye, Valerie E, Vogeley, Lutz, Aragao, David, Kenyon, Colin P, Shah, Syed T A, Doherty, Christine, Aherne, Margaret, Caffrey, Martin. Crystal structure of the integral membrane diacylglycerol kinase. NATURE[J]. 2013, 第 1 作者497(7450): 521-+, http://dx.doi.org/10.1038/nature12179.[46] Hopper, Jonathan T S, Yu, Yvonne TingChun, Li, Dianfan, Raymond, Alison, Bostock, Mark, Liko, Idlir, Mikhailov, Victor, Laganowsky, Arthur, Benesch, Justin L P, Caffrey, Martin, Nietlispach, Daniel, Robinson, Carol V. Detergent-free mass spectrometry of membrane protein complexes. NATURE METHODS[J]. 2013, 第 3 作者10(12): 1206-+, http://dx.doi.org/10.1038/NMETH.2691.[47] Liu, Wei, Wacker, Daniel, Gati, Cornelius, Han, Gye Won, James, Daniel, Wang, Dingjie, Nelson, Garrett, Weierstall, Uwe, Katritch, Vsevolod, Barty, Anton, Zatsepin, Nadia A, Li, Dianfan, Messerschmidt, Marc, Boutet, Sebastien, Williams, Garth J, Koglin, Jason E, Seibert, M Marvin, Wang, Chong, Shah, Syed T A, Basu, Shibom, Fromme, Raimund, Kupitz, Christopher, Rendek, Kimberley N, Grotjohann, Ingo, Fromme, Petra, Kirian, Richard A, Beyerlein, Kenneth R, White, Thomas A, Chapman, Henry N, Caffrey, Martin, Spence, John C H, Stevens, Raymond C, Cherezov, Vadim. Serial Femtosecond Crystallography of G Protein-Coupled Receptors. SCIENCE[J]. 2013, 第 0 作者342(6165): 1521-1524, http://dx.doi.org/10.1126/science.1244142.[48] Li, Dianfan, Boland, Coilin, Aragao, David, Walsh, Kilian, Caffrey, Martin. Harvesting and Cryo-cooling Crystals of Membrane Proteins Grown in Lipidic Mesophases for Structure Determination by Macromolecular Crystallography. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS[J]. 2012, 第 1 作者https://explore.openaire.eu/search/publication?articleId=od_______267::0534f5d537cc7881203bf6880c6469e7.[49] Li, Dianfan, Boland, Coiln, Walsh, Kilian, Caffrey, Martin. Use of a Robot for High-throughput Crystallization of Membrane Proteins in Lipidic Mesophases. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS[J]. 2012, 第 1 作者http://dx.doi.org/10.3791/4000.[50] Caffrey, Martin, Li, Dianfan, Dukkipati, Abhiram. Membrane Protein Structure Determination Using Crystallography and Lipidic Mesophases: Recent Advances and Successes. BIOCHEMISTRY[J]. 2012, 第 2 作者51(32): 6266-6288, http://dx.doi.org/10.1021/bi300010w.[51] Nederlof, Igor, Hosseini, Rohola, Georgieva, Dilyana, Luo, Jinghui, Li, Dianfan, Abrahams, Jan Pieter. A Straightforward and Robust Method for Introducing Human Hair as a Nucleant into High Throughput Crystallization Trials. CRYSTAL GROWTH & DESIGN[J]. 2011, 第 5 作者11(4): 1170-1176, http://dx.doi.org/10.1021/cg101374r.[52] Li, Dianfan, Caffrey, Martin. Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA[J]. 2011, 第 1 作者108(21): 8639-8644, http://dx.doi.org/10.1073/pnas.1101815108.[53] Li, Dianfan, Lee, Jean, Caffrey, Martin. Crystallizing Membrane Proteins in Lipidic Mesophases. A Host Lipid Screen. CRYSTAL GROWTH & DESIGN[J]. 2011, 第 1 作者11(2): 530-537, http://dx.doi.org/10.1021/cg101378s.
发表著作
(1) Lipid cubic phase for membrane protein X-ray crystallography, Springer, 2017-12, 第 2 作者
科研活动
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( 1 ) 磷脂酰肌醇合成酶的结构与功能, 主持, 国家级, 2016-01--2019-12( 2 ) 中组部“青年****”, 主持, 国家级, 2015-01--2017-12( 3 ) 上海市浦江人才计划, 主持, 省级, 2015-01--2016-12( 4 ) 基于上海同步辐射光源的跨膜蛋白鲨烯环氧酶结构与功能研究, 主持, 国家级, 2017-01--2019-12( 5 ) 脂酰转移酶的结构与功能及膜蛋白结晶前沿技术研究, 主持, 部委级, 2016-08--2020-12( 6 ) 脂代谢相关蛋白的免疫调控功能研究, 参与, 部委级, 2017-12--2022-12
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