Biochemistry and Molecular Biophysics
The Li lab studies the structural biology of membrane proteins important in cardiovascular biology and hematology. We have determined crystal structures of vitamin K epoxide reductase (VKOR), a key enzyme sustaining blood coagulation. VKOR is the target of warfarin, an oral anticoagulant used by 1% of the US population. We have also solved the first structure in the UbiA superfamily, which synthesizes lipophilic aromatic compounds that play essential roles in biological membranes. The structural insights of these proteins have allowed us to investigate deeply their biochemical properties and cellular functions using biochemistry, mass spectrometry, and cell biology approaches. The movie below shows how quniones such as vitamin K are made in membranes.
- Li S, Shen G, Li W. (2017) Intramembrane thiol oxidoreductases: evolutionary convergence and structural controversy. Biochemistry. Special issue: Future of biochemistry.
- Shen G, Cui W*, Zhang H, Zhou F, Huang W, Liu Q, Yang Y, Bowman GR, Sadler JE, Gross ML, Li W. (2017) Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer. Nature Structural & Molecular Biology 24, 69–76. Featured in News and Views, Nature Structural & Molecular Biology 24 5–6.
- Yang Y, Ke N, Liu S, Li W. (2017) Structural and biochemical analysis of intramembrane prenyltransferases in the UbiA superfamiIy. Methods in Enzymology. Enzymology at the Membrane Interface: Intramembrane Proteases, 584, 309-348.
- Li W. (2016) Bringing bioactive compounds into membranes: The UbiA superfamily of intramembrane aromatic prenyltransferases. Trends in Biochemical Sciences 41:356-370.
- Cheng W, Li W. (2014) Structural insights into ubiquinone biosynthesis in membranes. Science 343(6173):878-81.
- Liu S, Cheng W*, Fowle Grider R, Shen GM, and Li W. (2014) Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer. Nature Communications 5:3110.
- Park E., Mènètret JF, Gumbart JC, Ludtke SJ, Li W, Whynot A, Rapoport TA and Akey CW.(2014) Structure of the SecY channel during initiation of protein translocation. Nature 506:102-106.
- Li W, Li F. (2011) Cross-crystal averaging with search models to improve molecular replacement phases. Structure 19:155-161.
- Li W, Schulman S, Dutton R, Boyd D, Beckwith J, Rapoport TA. (2010) Structure of a bacterial homolog of vitamin K epoxide reductase. Nature, 463:507-512. Featured in Abstractions, Nature 463(7280):400.
- Schulman S, Wang B, Li W, Rapoport TA. (2010) Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners. Proc Natl Acad Sci U S A 107:15027-15032.
- Wu K, Li W*, Peng G, Li F. (2009) Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. Proc Natl Acad Sci U S A 106(47):19970-4.
- Li W, Schulman S, Boyd D, Erlandson K, Beckwith J, Rapoport TA. (2007) The plug domain of the SecY protein stabilized the closed state of the translocation channel and maintains a membrane seal. Molecular Cell 26:511-521. Cover story.
- Li W, Kamtekar S, Xiong Y, Sarkis GJ, Grindley ND, Steitz TA.(2005) Structure of a synaptic gamma delta resolvase tetramer covalently linked to two cleaved DNAs. Science 309:1210-1215.