1999-2004 B.S. University of Science and Technology of China
2004-2009 Ph.D. Purdue University, IN, USA

2017-present PI, School of Life Sciences, Peking University
2010-2017 Postdoc, Harvard Medical School
2009-2010 Postdoc, Purdue University

The laboratory focuses on transmembrane transport mechanisms of biological macromolecules such as protein and lipid molecules. The communication and regulation of cells and organelles with the outside needs to pass through the cell membranes. Therefore, transmembrane transport of biomacromolecules is a key step for cells to perform various physiological activities. Transmembrane transport is a dynamic, orderly, and tightly regulated process. At the molecular level, the specific interactions of proteins with phospholipid molecules control the transmembrane transport. A range of membrane proteins function as transporters and transport channels to maintain a dynamic balance of transmembrane transport. A large amount of clinical data show that many diseases are caused by mutations in transporters. Therefore, the molecular mechanisms for transmembrane transport will provide a key drug target for the treatment of related diseases. Our laboratory starts with a series of transport channels and transport enzymes, using biochemical and structural biology methods to reveal the cycle and regulation of its molecular transport.
In addition, the laboratory is committed to the development and application of Nanobody technology. Nanobodies are a class of single-chain, single-domain antibodies that are found mainly in Camelidae animals. Compared with traditional antibodies, Nanobodies have the advantages of simple structure, very stable, easy to express and mutation etc. We use the highly specific binding properties of Nanobodies to stabilize the intermediate state of protein complexes, thereby helping to study biochemical and structural biology. We will create a surface display platform to screen and optimize Nanobodies that are widely used in biotechnology and drug development.

• 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.

Laboratory Introduction