教育經曆:
1999-2004 本科，中國科學技術大學beat365
2004-2009 博士，普度大學生物系
工作經曆:
2017-至今 研究員，beat365官方网站
2017-至今 研究員，北大清華生命科學聯合中心
2010-2017 博士後，哈佛醫學院
2009-2010 博士後，普度大學生物系
執教課程:
生物化學讨論課
結構生物學
結構生物學實用方法
生物化學及分子生物學進展
定量分析技術
本實驗室主要研究以蛋白質、脂分子和核酸為代表的生物大分子的跨膜的運輸機制。細胞和細胞器與外界的交流和調控均需要通過細胞膜，因此生物大分子的跨膜運輸是細胞進行各項正常生理活動的關鍵步驟。跨膜運輸是一個動态，有序，并且受到嚴格調控的過程。在分子水平上，蛋白與磷脂分子的特異性相互作用控制着跨膜運輸。一系列膜蛋白行使轉運酶和轉運通道的功能，保持跨膜轉運的動态平衡。大量的臨床數據顯示，很多疾病是由轉運蛋白的突變引起的。因此，對跨膜轉運的分子機理研究将為相關疾病的治療提供關鍵的藥物靶點。我們實驗室從一系列轉運通道和轉運酶入手，利用生物化學和結構生物學的方法，力圖揭示其分子轉運的循環和調控過程。
此外，實驗室還緻力于發展和應用納米抗體技術。納米抗體是一類單鍊單結構域抗體，主要存在于駱駝科的動物體内。與傳統的抗體比較，納米抗體有結構簡單，非常穩定，易于表達與突變等優點。我們利用納米抗體高度特異性結合的特點來穩定蛋白複合物的中間狀态，從而幫助生化和結構生物學的研究。我們将建立表面展示平台，篩選和優化在生物技術和藥物開發上有廣泛應用的納米抗體。
• Ou X*, Ma C*, Sun D*, Xu J*, Wang Y*, Wu X, Wang D, Yang S, Gao N#, Song C#, Li L#. SecY translocon chaperones protein folding during membrane protein insertion. Cell. 2025 Feb 12; doi: 10.1016/j.cell.2025.01.037.
• Chen J, Zhou X, Yang Y, Li L. Protein translocation through alpha-helical channels and insertases. Structure. 2025 Jan 2;33(1):15-28. (Invited Review)
• Zhou X*, Yang Y*, Wang G*, Wang S*, Sun D, Ou X, Lian Y, Li L. Molecular pathway of mitochondrial preprotein import through the TOM-TIM23 supercomplex. Nat Struct Mol Biol. 2023 Dec;30(12):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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