教育经历:
1999-2004 本科，中国科学技术大学金沙集团wwW3354CC
2004-2009 博士，普度大学生物系
工作经历:
2017-至今 研究员，金沙集团wwW3354CC
2017-至今 研究员，北大清华生命科学联合中心
2010-2017 博士后，哈佛医学院
2009-2010 博士后，普度大学生物系
执教课程:
结构生物学
结构生物学实用方法
生物化学及分子生物学进展
定量分析技术
生物化学讨论课 本实验室主要研究生物大分子，例如蛋白和脂分子，的跨膜的运输机制。细胞和细胞器与外界的交流和调控均需要通过细胞膜，因此生物大分子的跨膜运输是细胞进行各项正常生理活动的关键步骤。跨膜运输是一个动态，有序，并且受到严格调控的过程。在分子水平上，蛋白与磷脂分子的特异性相互作用控制着跨膜运输。一系列膜蛋白行使转运酶和转运通道的功能，保持跨膜转运的动态平衡。大量的临床数据显示，很多疾病是由转运蛋白的突变引起的。因此，对跨膜转运的分子机理研究将为相关疾病的治疗提供关键的药物靶点。我们实验室从一系列转运通道和转运酶入手，利用生物化学和结构生物学的方法，力图揭示其分子转运的循环和调控过程。
此外，实验室还致力于发展和应用纳米抗体技术。纳米抗体是一类单链单结构域抗体，主要存在于骆驼科的动物体内。与传统的抗体比较，纳米抗体有结构简单，非常稳定，易于表达与突变等优点。我们利用纳米抗体高度特异性结合的特点来稳定蛋白复合物的中间状态，从而帮助生化和结构生物学的研究。我们将建立表面展示平台，筛选和优化在生物技术和药物开发上有广泛应用的纳米抗体。
• Zhou X*, Yang Y*, Wang G*, Wang S*, Sun D, Ou X, Lian Y, Li L. (2023) Molecular pathway of mitochondrial preprotein import through the TOM-TIM23 supercomplex. Nat Struct Mol Biol. 30, 1996-2008.
• Dong L, Yang S, Chen J, Wu X, Sun D, Song C, Li L. Structural basis of SecA-mediated protein translocation. PNAS. 2023 Jan 4; 120 (2) e2208070120.
• Xu J, He Y, Wu X, Li L. Conformational changes of a phosphatidylcholine flippase in lipid membranes. Cell Reports. 2022 Mar 15; 2022(38), 110518.
• Zhang Y, Ou X, Wang X, Sun D, Zhou X, Wu X, Li Q, Li L. Structure of the mitochondrial TIM22 complex from yeast. Cell Research 2021; 31:366–368.
• He Y, Xu J, Wu X, Li L. Structures of a P4-ATPase lipid flippase in lipid bilayers. Protein&Cell. 2020; 11(6):458-463. (Recommended by Faculty Opinions)
• Ma C, Wu X, Sun D, Park E, Catipovic MA, Rapoport TA, Gao N, Li L. Structure of the substrate-engaged SecA-SecY protein translocation machine. Nature Communications. 2019 Jun 28; 10(1): 1-9. (Recommended by Faculty Opinions)
• Rapoport TA, Li L, and Park E. Structural and Mechanistic Insights into Protein Translocation. Annu Rev Cell Dev Biol. 2017; 33:369–390.
• Li L*#, Park E*, Ling J, Ingram J, Ploegh H, Rapoport TA#.Crystal structure of a substrate-engaged SecY protein-translocation channel. Nature. 2016 Mar 17; 531(7594):395-9. (* equal contribution; # co-corresponding authors)
• Li L, Fierer JO, Rapoport TA, Howarth M. Structural analysis and optimization of the covalent association between SpyCatcher and a peptide Tag. J Mol Biol. 2014 Jan 23; 426(2):309-17.
• Yun SI, Song BH, Kim JK, Yun GN, Lee EY, Li L, Kuhn RJ, Rossmann MG, Morrey JD, Lee YM. A molecularly cloned, live-attenuated Japanese encephalitis vaccine SA14-14-2 virus: a conserved single amino acid in the ij Hairpin of the Viral E glycoprotein determines neurovirulence in mice. PLoS Pathog. 2014 Jul 31; 10(7):e1004290.
• Wang Z, Li L, Pennington JG, Sheng J, Yap ML, Plevka P, Meng G, Sun L, Jiang W, Rossmann MG. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. J Virol. 2013 Aug; 87(16):8909-15.
• Li L, Jose J, Xiang Y, Kuhn RJ, Rossmann MG. Structural changes of envelope proteins during alphavirus fusion. Nature. 2010 Dec 2; 468(7324):705-8. (Cover image of the issue)
• Xiang Y, Leiman PG, Li L, Grimes S, Anderson DL, Rossmann MG. Crystallographic insights into the autocatalytic assembly mechanism of a bacteriophage tail spike. Mol Cell. 2009 May 15; 34(3):375-86.
• Zhou Z, Khaliq M, Suk JE, Patkar C, Li L, Kuhn RJ, Post CB. Antiviral compounds discovered by virtual screening of small-molecule libraries against dengue virus E protein. ACS Chem Biol. 2008 Dec 19; 3(12):765-75.
• Li L, Lok SM, Yu IM, Zhang Y, Kuhn RJ, Chen J, Rossmann MG. The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science. 2008 Mar 28; 319(5871):1830-4.
• Yu IM, Zhang W, Holdaway HA, Li L, Kostyuchenko VA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J. Structure of the immature dengue virus at low pH primes proteolytic maturation. Science. 2008 Mar 28; 319(5871):1834-7.
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