BNL Home

Qun Liu

Principal Investigator

Background

Qun Liu obtained his Ph.D. in biophysics from Cornell University (2006) and did his postdoc research at Cornell Synchrotron Light Source (CHESS). After his postdoc training, in 2009 he became a scientist at the New York Structural Biology Center; there he worked at the New York Consortium on Membrane Protein Structure as well as the X4 beamlines at the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory. In 2015 Qun Liu joined the Biology Department of the Brookhaven National Laboratory as a Principle Investigator with a joint appointment from NSLS-II. Qun Liu is an Adjunct Professor and a faculty member of the Biochemistry and Structural Biology Program at Stony Brook University.

Research Interests

Membrane protein structural biology

Membrane proteins form specialized gates connecting intracellular compartments and external environment, and are central for understanding information flux (for example, metabolites, nutrients, ions, and electrons) across membranes. Structural studies of these transmembrane gates and their functional characterizations may provide insights into understanding their roles in physiology and pathology. Our structural biology research focuses on the structures and mechanisms of important membrane proteins and their complexes. One interest is to study structures and mechanisms of TMBIM (Transmembrane BAX Inhibitor-1 Motif-containing) proteins in protection of cellular life from stress. TMBIM proteins were defined by sequence relationships to Bax inhibitor-1 (BI-1 or TMBIM6), which was discovered as a gene product capable of blocking Bax-induced stress in yeast. The TMBIM proteins are highly hydrophobic and essentially ubiquitous, present in prokaryotes, fungi, plants, and metazoan animals, including invertebrates and mammals. Human has six and plant Arabidopsis thaliana has seven TMBIM proteins with versatile cellular localizations to ER, Golgi, endosome, lysosome and mitochondrion. By using x-ray crystallography combined with cell- and proteoliposome-based flux assays, our group has determined a bacterial homolog structure in multiple conformational states (Figure 1) and characterized the novel pH-sensitive calcium channel activity. Structures determine functions. We are interested in understanding the molecular mechanisms of how TMBIM proteins respond to stress in protection of life. With the accumulated knowledge from this family and their interacting partners, ultimately, experimental strategies may be enabled to reprogram cells for real-life applications.

Technology research and development

We are also interested in developing technologies that will enable or facilitate the membrane protein research. Different from soluble proteins, membrane proteins have hydrophobic transmembrane segments within and hydrophilic heads out of the lipid bilayer, respectively. Stabilization of membrane proteins for structural and functional characterization remains challenging. Eukaryotic membrane proteins are even more challenging owing to prevalent post-modifications and their different cellular localizations. The requirements of specialized lipids and compartments further complicate the accessibility to structural and functional studies. Consequently, structure determinations of eukaryotic membrane proteins and their complexes are never easy. To overcome these barriers, we are developing technologies by leveraging BNL capabilities of x-ray photon sciences at NSLS-II, nanotechnology and cryo electron microscopy at Center for Functional Nanomaterials (CFN), and data-driving discovery at Computational Science Initiative (CSI).

Recent News

Selected Publications

(*corresponding author; a full list at Google Scholar)

  • Guo, G., Zhu. P., Fuchs, M.R., Shi, W., Andi, B., Gao, Y., Hendrickson, W.A., McSweeney, S., *Liu, Q. (2019). Synchrotron microcrystal native-SAD phasing at a low energy. IUCrJ 6, 532-542. (cover)
  • Guo, G., Xu, M., Chang, Y., Luyten, T., Seitaj, B., Liu, W., Zhu, P., Bultynck, G., Shi, L., Quick, M., *Liu, Q. (2019). Ion and pH Sensitivity of a TMBIM Ca2+ Channel. Structure 27, 1013-1021. (cover)
  • Guo, G., Fuchs, M.R., Shi, W., Skinner, J., Berman, E., Ogata, C. M., Hendrickson, W.A., McSweeney, S., *Liu, Q. (2018). Sample manipulation and data assembly for robust microcrystal synchrotron crystallography. IUCrJ 5, 238-246.
  • Sanghai, Z.A., Liu, Q., Clarke, O.B., Belcher-Dufrisne, E.L.M., Wiriyasermkul, P., Giese, M.H., Pinto, E.L., Kloss, B., Tabuso, S., Love, J., Punta, M., Banerjee, S., Rajashankar, K.R., Rost, B., Logothetis, D., Quick, M., Hendrickson, W.A., and Mancia, F. (2018).  Structure-based analysis of CysZ-mediated cellular uptake of sulfate. eLife 7, e27829.
  • *Liu, Q. (2017). TMBIM-mediated Ca2+ homeostasis and cell Death. Mol. Cell. Res. 1864, 850-857.
  • *Liu, Q., *Hendrickson, W. A. (2017). Contemporary use of anomalous diffraction in biomolecular structure analysis. Methods Mol. Biol. 1607, 377-399.
  • Hu, M., Zhang, H., Liu, Q., *Hao, Q. (2016). Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion. Sci. Report 6, 38655, DOI: 10.1038/srep38655.
  • Yu, H., Takeuchi, H., Takeuchi, M., Liu, Q., Kantharia, J., *Haltiwanger, R. S., *Li, H. (2016) Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Nat. Chem. Biol. 12, 735-740.
  • *Liu, Q. and *Hendrickson, W.A. (2015). Crystallographic phasing from weak anomalous signals. Curr. Opin. Struct. Biol. 34, 99-107.
  • *Liu, Q., Guo, Y., Chang, Y., Cai, Z., Assur, Z., Mania, F., Greene, M., *Hendrickson, W. A. (2014). Multi-crystal native SAD analysis at 6 keV. Acta Cryst. D70, 2544-2557.
  • Chang, Y., Bruni, R., Kloss, B., Assur, Z., Kloppmann. E., Burkhard, R., Hendrickson, W. A., *Liu, Q. (2014). Structural basis for a pH-sensitive calcium leak across membranes. Science 344, 1131-1135.
  • Yang, T., Liu, Q., Kloss, B., Renato, B., Kalathur, R., Guo, Y., Kloppmann, E., Rost, B., Colecraft, H. M., and *Hendrickson, W. A. (2014). Structure and selectivity in bestrophin ion channels. Science 346, 355-359.
  • Liu, Q., Liu, Q. L., *Hendrickson, W. A. (2013). Robust structural analysis of native biological macromolecules from multi-crystal anomalous diffraction data. Acta Cryst. D69, 1314-1332.
  • Qi, R., Sarbeng. E.B., Liu, Q., Le, K. Q, Xu, X., Xu, H., Yang, J., Wong, J. L., Vorvis, C., Hendrickson, W. A., Zhou, L., *Liu, Q.L. (2013) Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP. Nat. Struct. Mol. Biol. 20, 900-907.
  • Mancusso, R. Gregorio, G.G., Liu, Q., *Wang, D.-N. (2012). Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter. Nature 491, 622-626.
  • Liu, Q., Dahmane, T., Zhang, Z., Assur, Z., Brasch, J., Shapiro, L., Mancia, F., *Hendrickson, W. A. (2012). Structures from anomalous diffraction of native biological macromolecules. Science 336, 1033-1037.
  • Liu, Q., Zhang, Z. *Hendrickson, W. A. (2011). Multi-crystal anomalous diffraction for low-resolution macromolecular phasing. Acta Cryst. D67, 45-59. (Cover)
  • Liu, Q. Graeff, R., Kriksunov,I.A., Jiang,H., Zhang,B., Oppenheimer, N., Lin, H., Potter, B.V.L. *Lee, H.C., *Hao, Q. (2009). Structural basis for enzymatic evolution from a dedicated ADP-ribosyl cyclase to a multi- functional NAD hydrolase. J. Biol. Chem. 284, 27637-27645.
  • Liu, Q., Kriksunov, I.A., Jiang, H., Graeff, R. Lin, H., *Lee, H.C., and *Hao, Q. (2008) Covalent and non-covalent intermediates of an NAD utilizing enzyme, human CD38. Chem. Biol. 15, 1068-1078.
  • Liu, Q., Kriksunov, I.A., Moreau, C., Graeff, R., Potter, B.V.L. *Lee, H.C., and *Hao, Q (2007). Catalysis associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog. J. Biol. Chem. 282, 24825-24832.
  • Liu, Q., Kriksunov, I. A., Graeff, R., *Lee, H.C. and *Hao, Q. (2007). Structural basis for formation and hydrolysis of calcium messenger cyclic ADP-ribose by human CD38. J. Biol. Chem. 282, 5853-5861.
  • Liu, Q., Kriksunov, I.A., Graeff, R. Munshi, C., *Lee, H.C. and *Hao, Q. (2006). Structural basis for the mechanistic understanding human CD38 controlled multiple catalysis. J. Biol. Chem. 281, 32861-32869.
  • Liu, Q., Kriksunov, I. A., Graeff, R., Munshi, C., *Lee, H. C., and *Hao, Q. (2005). Crystal structure of human CD38 extracellular domain. Structure 13, 1331-1339. (Cover)
  • Liu, Q., Huang, Q., Lei, X.G., and *Hao, Q. (2004). Crystallographic snapshots of Aspergillus fumigatus phytase, revealing its enzymatic dynamics. Structure 12, 1575-1583.
  • Liu, Q., Weaver, A.J., Xiang, T., Thiel, D.J. and *Hao, Q. (2003). Low-resolution molecular replacement using a six-dimensional search. Acta Cryst. D59, 1016-1019.
  • Liu, Q., Huang, Q., *Teng, M.K., Weeks, C.M., Jelsch, C., Zhang, R. and *Niu, L.W. (2003). The crystal structure of a novel, inactive, lysine 49 PLA2 from Agkistrodon acutus venom: an ultrahigh resolution, AB initio structure determination. J. Biol. Chem. 278, 41400-41408.