Centrioles; Crystallography, X-Ray; Parasites; Photoreceptor Connecting Cilium; Plasmodium falciparum; Secretory Vesicles; Structural Homology, Protein; Toxoplasma; Vesicular Transport Proteins
- Structural biology of ciliogenesis and membrane trafficking
Research Area: Our research focuses on three main topics: ciliogenesis, parasitology, and membrane trafficking.
We are a structural biology group investigating structures of proteins and protein complexes with essential roles in eukaryotic cells. One focus of our group is structural characterization of proteins involved in the biogenesis of centrioles and cilia, which are two eukaryotic organelles essential for cytokinesis and cell motility/signaling. Both centriole and cilium have been linked to many cancers and numerous ciliopathies. We aim to provide a high-resolution structural view of centriolar assembly so as to shed light on protein functions in ciliogenesis. The other focus of our work is on parasites. In collaboration with several parasitology groups around the world, we have embarked on structural studies of a few critical proteins for the survival of human parasites including Traypanosoma brucei, Toxoplama gondii and Plasmodium falciparum.
Techniques, methods & infrastructure
Technically, we mainly use X-ray crystallography to determine the structures of the target proteins and their complexes. Other biophysical techniques such as thermofluor assays, circular dichroism (CD), isothermal titration calorimetry(ITC), static/dynamic light scattering (SLS/DLS), and analytical ultracentrifugation will as well be employed to study the architecture and assembly of the proteins and their complexes. Small proteins and domains are also studied by nuclear magnetic resonance (NMR) spectroscopy, whereas large assemblies are examined by electron microscopy (EM). Our structural studies will be complemented by site-directed mutagenesis, in vitro biochemical experiments, and in vivo assays (mostly with our collaborators) to test our mechanistic hypotheses. The available new structures will enhance our understanding of how the proteins function and provide hints as to how their malfunction leads to human diseases.
- Shimanovskaya, E. et al., 2014. Structure of the C. elegans ZYG-1 cryptic polo box suggests a conserved mechanism for centriolar docking of Plk4 kinases. Structure, 22(8), pp.1090-1104. Available at: http://dx.doi.org/10.1016/j.str.2014.05.009.
- Vidilaseris, K. et al., 2014. Assembly Mechanism of Trypanosoma brucei BILBO1, a Multidomain Cytoskeletal Protein. Journal of Biological Chemistry, 289(34), pp.23870-23881. Available at: http://dx.doi.org/10.1074/jbc.M114.554659.
- Qiao, R. et al., 2012. SAS-6 coiled-coil structure and interaction with SAS-5 suggest a regulatory mechanism in C. elegans centriole assembly . The EMBO Journal, 31(22), pp.4334-4347. Available at: http://dx.doi.org/10.1038/emboj.2012.280.
- Dong, G. et al., 2009. Insights into MHC Class I Peptide Loading from the Structure of the Tapasin-ERp57 Thiol Oxidoreductase Heterodimer. Immunity, 30(1), pp.21-32. Available at: http://dx.doi.org/10.1016/j.immuni.2008.10.018.
- Dong, G, et al., 2007. A catalytic coiled-coil: structural insights into the activation of the Rab GTPase Sec4p by Sec2p. Mol. Cell, 25, pp.455-462. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17289591.