Li laboratory studies the structure and function of integral membrane proteins, with a focus on ones that are important for hematologic and cardiovascular systems. We use a variety of structural biology, biochemistry, cell biology and mass spectrometry techniques to understand the structural mechanism of these membrane proteins. Structural insights give us a novel angle to elucidate the actions of these proteins in cellular settings. Deep understanding of protein structure and function often has implications significant for human disease. In addition, these proteins provide challenges that motivate us to develop new structural and biochemical methods broadly applicable to membrane biology.

Selected Publications

  • S. Liu, S. Li, G. Shen, N. Sukumar, A. M. Krezel, W. Li, Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science 371(6524):eabc5667. (2021). Abstract. Reprint.
  • S. Liu, S. Li, Y. Yang, W. Li, Termini restraining of small membrane proteins enables structure determination at near-atomic resolution. Science Advances. 6(51):eabe3717. (2020).
  • Y. Yang, X. R. Liu, Z. J. Greenberg, F. Zhou, P. He, L. Fan, S. Liu, G. Shen, T. Egawa, M. L. Gross, L. G. Schuettpelz, W. Li, Open conformation of tetraspanins shapes interaction partner networks on cell membranes. EMBO Journal 39, e105246 (2020).
  • G. Shen, W. Cui, H. Zhang, F. Zhou, W. Huang, Q. Liu, Y. Yang, S. Li, G. R. Bowman, J. E. Sadler, M. L. Gross, W. Li, Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer. Nature Structural & Molecular Biology 24, 69-76 (2017). Featured in News and Views, Nature Structural & Molecular Biology 24 5–6.
  • W. Li, Bringing Bioactive Compounds into Membranes: The UbiA Superfamily of Intramembrane Aromatic Prenyltransferases. Trends in Biochemical Sciences 41, 356-370 (2016).
  • S. Liu, W. Cheng, R. Fowle Grider, G. Shen, W. Li, Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer. Nature Communications 5, 3110-3110 (2014).
  • W. Cheng, W. Li, Structural insights into ubiquinone biosynthesis in membranes. Science 343, 878-881 (2014).
  • W. Li, S. Schulman, R. J. Dutton, D. Boyd, J. Beckwith, T. A. Rapoport, Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463, 507-512 (2010).
  • W. Li, S. Schulman, D. Boyd, K. Erlandson, J. Beckwith, T. A. Rapoport, The Plug Domain of the SecY Protein Stabilizes the Closed State of the Translocation Channel and Maintains a Membrane Seal. Molecular Cell 26, 511-521 (2007).
  • W. Li, S. Kamtekar, Y. Xiong, G. J. Sarkis, N. D. Grindley, T. A. Steitz, Structure of a synaptic gammadelta resolvase tetramer covalently linked to two cleaved DNAs. Science 309, 1210-1215 (2005).