California NanoSystems Institute

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Z. Hong Zhou, Ph.D.

Director, Electron Imaging Center for NanoMachines (EICN)

Professor, Microbiology, Immunology & Molecular Genetics

Member, ACCESS Program: Dept. of Microbiology, Immunology, & Molecular Genetics, ACCESS, California NanoSystems Institute

Education:

Degrees:

Ph.D., Baylor College of Medicine, 1995
M.S.

Honors and Awards:

2004 American Microscopy Society, Burton Award
2002 American Heart Association, Established Investigator Award
2000 March of Dimes Foundation, Basil O'Connor Scholar Award
1999 Pew Scholar in the Biomedical Sciences, Pew Scholar in the Biomedical Sciences

Contact Information:

Email Address:	Hong.Zhou@ucla.edu

Home Page:	http://www.eicn.ucla.edu/

Technical Research Interest:

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.

Additional Information:

Z. Hong Zhou, Ph. D. Professor Hong Zhou is a Professor in UCLA's Microbiology, Immunology, and Molecular Genetics department. Dr. Zhou's research centers on studying the assembly and structures of viruses and macromolecular complexes using cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET), with focus on pushing the resolution of cryoEM to atomic resolution. To this end, he combines expertise in structural virology, computational biology, and bioinformatics. He was a Pew Scholar in the Biomedical Sciences, holds the Basil O'Connor Scholar Award, the Established Investigator Award, and the Burton award.

Selected Publications:

Yu, X., Hiromasa, Y., Tsen, H., Stoops, J.K., Roche, T.E., Zhou, Z.H., Structures of the Human Pyrucate Dehydrogenase Complex Cores: a Highly Conserved Catalytic Center with Flexible N-terminal Domains., Structure, 2008, 16 (1), 104-114.

Deng, B., O'Connor, C.M., Kedes, D.H. and Zhou, Z.H., Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation, Journal of Structural Biology, 2008, 161 (3), 419-427.

Jiang, J., Zhang, X., Chen, Y., Wu, Y., Zhou, Z.H., Chang, Z. and Sui, S.F., Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins, Proceedings of the National Academy of Sciences USA, 2008, (33) (105), 11939-44.

Cheng, L. Fang, Q. Shah, S. Atanasov, I. C. Zhou, Z. H. , Subnanometer-resolution structures of the grass carp reovirus core and virion, J Mol Biol, 2008, 382 (1), 213-22.

Liu, H., Cheng,L., Zeng, S., Cai, C., Zhou,Z.H., Yang, Q., Symmetry-adapted spherical harmonics method for high-resolution 3D single-particle reconstructions, Journal of Structural Biology, 2008, 161, 64-73.

Zhou, Z. H. , Towards atomic resolution structural determination by single-particle cryo-electron microscopy, Curr Opin Struct Biol, 2008, 18 (2), 218-28.

Dai, W., Jia, Q., Bortz, E., Shah, S., Liu, J., Atanasov, I., Li, X., Taylor, D.A., Sun, R. and Zhou, Z.H., Unique stuctures of a tumor herpesvirus revealed by cryo-electron tomography and microscopy, Journal of Structural Biology, 2008, 161, 428-438.

Xuekui Yu, Lei Jin, & Z. Hong Zhou, 3.88 A structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy, Nature, 2008, 453, 415-419.

Cheng, L., Fang, Q., Shah, S., Atanasov, I.C. and Zhou, Z.H., Subnanometer-Resolution Structures of the Grass Carp Reovirus Core and Virion , Journal Mol. Biology, 2008, 1 (382), 213-22.

Yu, X Qiao, M Atanasov, I Hu, Z Kato, T Liang, TJ Zhou, ZH, Cryo-electron microscopy and three-dimensional reconstructions of hepatitis C virus particles., Virology, 2007, 367 (1), 126-134.

Zhou, Z. H., Cypovirus, In Structure and Molecular Biology of Segmented Double-Stranded RNA Viruses, P.J.T. and M. L. Nibert eds., Horizon Scientific Press, 2007.

Deng, B O'Connor, CM Kedes, DH Zhou, ZH, Direct visualization of the putative portal in the Kaposi's sarcoma-associated herpesvirus capsid by cryoelectron tomography., Journal of virology, 2007, 81 (7), 3640-4.

Liu, F. and Zhou, Z.H., Comparative virion structures of human herpesviruses. In Human Herpesviruses: Biology, Therapy and Immunoprophylaxis, Arvin, A., Campadelli-Fiume, G., Moore, P., Mocarski, E., Roizman, B., Whitley, R., & Yamanishi, K., eds., Cambridge University Press, 2006, 27-43.

Zhou, Z. H.*, Stoops, JK, Krueger, Ultrastructure and Assembly of Human Herpesvirus-6 (HHV-6), In Human Herpesvirus-6, Krueger/Alashi (eds.), Elsevier Science Publishers, 2006, 11-21.

Yu, X Trang, P Shah, S Atanasov, I Kim, YH Bai, Y Zhou, ZH Liu, F, Dissecting human cytomegalovirus gene function and capsid maturation by ribozyme targeting and electron cryomicroscopy., Proceedings of the National Academy of Sciences of the United States of America, 2005, 102 (20), 7103-8.

Yu, X Shah, S Atanasov, I Lo, P Liu, F Britt, WJ Zhou, ZH, Three-dimensional localization of the smallest capsid protein in the human cytomegalovirus capsid., Journal of Virology, 2005, 79 (2), 1327-32.

Wan, Y., Chiu, W., Zhou, Z.H., Full contrast transfer function correction in 3D cryo-EM reconstruction, IEEE Proceedings of ICCCAS, 2004, 960-964.

Baker, ML Jiang, W Bowman, BR Zhou, ZH Quiocho, FA Rixon, FJ Chiu, W, Architecture of the herpes simplex virus major capsid protein derived from structural bioinformatics., Journal of molecular biology, 2003, 331 (2), 447-56.

Kong, Y., Ming, D., Wu, Y., Stoops, J.S., Zhou, Z.H., Ma, J., Conformational flexibility of pyruvate dehydrogenase complexes, J. Mol. Biol., 2003, 330, 129-135.

Zhou, Z.H.*, Zhang, H., Jakana, J., Lu, X.Y., Zhang, J.Q. , Cytoplasmic polyhedrosis virus structure at 8 Å by electron cryomicroscopy: structural basis of capsid stability and mRNA processing regulation, Structure, 2003, 11 (6), 651-663.

Bortz, E. Whitelegge, J. P. Jia, Q. Zhou, Z. H. Stewart, J. P. Wu, T. T. Sun, R. , Identification of proteins associated with murine gammaherpesvirus 68 virions, J Virol, 2003, 77 (24), 13425-32.

Lu, BY Atanasov, I Zhou, ZH Chang, JY, Reversible aggregation of mouse prion protein derivatives with PrPSC-like structural properties., Journal of protein chemistry, 2003, 22 (2), 115-26.

Zhou, Z.H.*, Stoops, J.K. and Reed, L.J., Structural and functional organization of pyruvate dehydrogenase complexes. In: Thiamine, Jordan F. & Patel M.S. (eds), Jordan F. & Patel M.S. (Eds), 2003, 309-330.

Xia, Q., Jakana, J., Zhang, J.-Q., Zhou, Z.H., Structural comparisons of empty and full CPV: protein-RNA interactions and implications for endogenous RNA transcription mechanisms, J. Biol. Chem., 2003, 278, 1094-1100.

Zhou, Z.H.* and Chiu, W., Structural determination of icosahedral viruses by electron cryomicroscopy at subnanometer resolution, Advances in Protein Chemistry, 2003, 64, 93-124.

Lo, P., Yu, X., Atanasov, I., Chandran, B., Zhou, Z.H., Three-dimensional localization of pORF65 in Kaposi's sarcoma-associated herpesvirus capsid, J. Virol., 2003, 77, 4221-4230.

Yu, X.K., O'Connor, C.M., Atanasov, I., Damania, B., Kedes, D.H., Zhou, Z.H., Three-dimensional structures of the A, B, and C capsids of Rhesus monkey Rhadinovirus, J. Virol., 2003, 77, 13182-13193.

Zhou, Z. H., Zhang, H., Jakana, J., Lu, X.Y., Zhang, J.Q., Cytoplasmic Polyhedrosis Virus Structure at 8 A by Electron ryomicoscopy: Structural Basis of Capsid Stability and mRNA Processing Regulation, Structure, 2003, 11 (6), 651-663.

Dai, W Liang, Y Zhou, ZH, Web portal to an image database for high-resolution three-dimensional reconstruction., Journal of structural biology, 2003, 144 (1-2), 238-45.

Chiu, W., Baker, M.L., Jiang, W., Zhou, Z.H., Deriving folds of macromolecular complexes through electron cryomicroscopy and bioinformatics, Curr. Opin. Struct. Biol., 2002, 12(2), 263-269.

Liang, Y., Ke, E.Y., Zhou, Z.H., IMIRS: a high-resolution 3D reconstruction package integrated with a relational image database, J. Struct. Biol., 2002, 137, 292-304.

Zhang, H Yu, XK Lu, XY Zhang, JQ Zhou, ZH, Molecular interactions and viral stability revealed by structural analyses of chemically treated cypovirus capsids., Virology, 2002, 298 (1), 45-52.