|Structureand fucntion of molecular complexes, viruses and cellular machineries
Professor Hong Zhou’s lab focuses on 3D structural studies of biological complexes using cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). These emerging methods are particularly suitable for structure determination of large molecular complexes, viruses, celluar machineries and bacterial cells. Recent efforts have focuses on developong and applying advanced cryoEM and cryoET techniques to visualize the dynamic processes of microbial infections and to decepher the mechanisms of fundamental biological processes. Dr. Zhou’s group is at the forefront in pushing the envelope of cryoEM reconstruction to atomic resolution.
|Recent advances have given cryo-electron microscopy and single-particle reconstruction (“cryoEM”) an increasingly important role in determining, at 4-7 Å resolution, the 3D structures of macromolecular complexes or biological nanomachines (~150 kDa and 10 nm in dimension). At this resolution, secondary structural elements and bulky amino-acid side chains are readily resolved and can be used to build pseudoatomic models of its subunits for understanding molecular interactions. The emerging method of cryo-electron tomography (cryoET) allows the determination of three dimensional architectures of objects ranging in size from a nanometer to micrometers. These structural methods provide exciting opportunities to determine the structures of microbes and subcellular assemblies that are either too large or too heterogeneous to be investigated by conventional crystallographic or NMR methods. Research in my laboratory aims to understand the mechanisms governing macromolecular functions by pushing the resolution limit of cryoEM to near-atomic resolution and by describing large, pleomorphic, dynamic structures or conformations using the integrative approach of cryoEM and cryoET. The long-term goal of our research is to study their structures and mechanisms of actions by an integrative approach using cryoEM/cryoET, bioinformatics modeling and high performance computing. Current efforts focus on three intermediate projects toward our goal: 1, to develop integrative techniques for atomic resolution cryoEM structural determination; 2, to decipher the mechanisms of actions of multi-enzyme complexes and multi-component nanomachines, such as human pyruvate dehydrogenase complexes; 3, to establish a 3D atlas of key events leading to the assembly and host infection of tumor herpesviruses.
- Buehler D.C., Toso D.B., Kickhoefer V.A., Zhou Z.H., Rome L.H., “Vaults Engineered for Hydrophobic Drug Delivery,” Small. 2011. (Epub ahead of print)
- Zhang X., Jin L., Fang Q., Hui W.H., Zhou Z.H., “3.3 A Cryo-EM Structure of Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry,” Cell. 2010;131(3):472-82.
- Yan M., Du J., Zhen G., Liang M., Hu Y., Zhang W., Priceman S., Wu L., Zhou Z.H., Liu Z., Segura T., Tang Y., Lu Y., “A novel intracellular protein delivery platform based on single-protein nanocapsules,” Nature Nanotechnology. 2010;5:48-53.
- Liu H., Jin L., Koh S.B.S., Atansov I., Schein S., Wu L. Zhou Z.H., “Atomic Structure of Human Adenovirus by Cryo-EM REveals Interactions Among Protein Networks,” Science. 2010;329(5995):1038-43.
- Zhang X., Boyce M., Bhattacharya B., Zhang .X, Schein S., Roy P., Zhou Z.H., “Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins,” PNAS. 2010;107(13):6292-7.
- Zhu J., Cheng L., Fang Q., Zhou Z.H., Honig B., “Building and Refining Protein Models within Cryoelectron Microscopy Density maps Based on Homology Modeling and Multiscale Structure Refinement,” Journal of Molecular Biology. 2010;327(5966).
- Liu J., Howell J.K., Bradley S.D., Zheng Y., Zhou Z.H., Norris S.J., “Cellular architecture of Treponemapallidum: novel flagellum, periplasmic cone, and cell envelope as revealed by cryo electron tomography,” J Mol Biol. 2010;403(4):546-61.
- Leong P.A., Yu X., Zhou Z.H., Jensen G.J., “Correcting for the ewald sphere in high-resolution single-particle reconstructions,” Methods Enzymol. 2010;428:369-8.
- Ge, P., Tsao, J., Schein, S., Green, T.J., Luo, M., Zhou, Z.H. , “Cryo-EM Model of the Bullet-Shaped Vesicular Stomatitis Virus,” Science. 2010;327(5966):689-93.
- Huang C.S., Sadre-Bazzaz K., Shen Y., Deng B., Zhou Z.H., Tong L., “Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase,” Nature. 2010;466(7309):1001-5.