Cryogenic Electron Microscopy (CryoEM)

Cryogenic electron microscopy (cryoEM) is a powerful technique that allows us to study biological specimens that are preserved by freezing in vitreous ice. A solution containing a sample of the imaging target is applied to a grid and rapidly frozen using liquid ethane or a mixture of liquid ethane and propane. A TEM is used to collect micrographs in which particle images are 2D projections of the original 3D object. Emplying a complex computational workflow termed single-particle analysis (SPA), we are able to extract particles from micrographs, assort them into classes, and ultimately produce a high-resolution 3D structure of our imaging target.

Although cryo-EM development began in the 1970s, recent advancements in detectors and software have revolutionized the field, allowing the determination of biomolecular structures at nearly atomic resolution. This approach has gained widespread attention as an alternative to X-ray crystallography and NMR spectroscopy for determining the structures of large molecules without the need for crystallization. In 2017, Jacques Dubochet, Joachim Frank, and Richard Henderson were awarded the Nobel Prize in Chemistry for their pioneering work in cryo-electron microscopy, which enables high-resolution structure determination of biomolecules in solution. Additionally, cryoEM was recognized as the "Method of the Year" by Nature Methods in 2015.

Our lab has specialized in using cryoEM to study the viral structures, augmenting out insight into the molecular basis and viral pathogenesis and informing future structure-based design of antiviral therapeutics. Below are displayed some of our lab’s and our collaborators’ most notable works on the front of cryoEM.

Select publications:
Cryo-EM structure of the mature dengue virus at 3.5-Å resolution .
Zhang, X., Ge, P., Yu, X., Brannan, J. M., Bi, G., Zhang, Q., Schein, S. & Zhou, Z. H. (2013). Nature Structural & Molecular Biology
Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein Networks.
Liu, H., Jin, L., Koh, S. B. S., Atanasov, I., Schein, S., Wu, L. & Zhou, Z. H. (2010). Science
Seeing the Herpesvirus Capsid at 8.5Å.
Zhou, Z. H., Dougherty, M., Jakana, J., He, J., Rixon, F. J. & Chiu, W. (2000). Science

Structure of Tetrahymena telomerase-bound CST with polymerase α-primase.
He, Y., Song, H., Chan, H., Liu, B., Wang, Y., Sušac, L., Zhou, Z. H. & Feigon, J. (2022). Nature
Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein Networks.
Zhang, X., Jin, L., Fang, Q., Hui, W. H. & Zhou, Z. H. (2010). Cell
Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel.
Li, B., Ge, P., Murray, K. A., Sheth, P., Zhang, M., Nair, G., Sawaya, M. R., Shin, W. S., Boyer, D. R., Ye, S., Eisenberg, D. S., Zhou, Z. H. & Jiang, L. (2018). Nature Communications
Visualization of Tegument-Capsid Interactions and DNA in Intact Herpes Simplex Virus Type 1 Virions.
Zhou, Z. H., Chen, D. H., Jakana, J., Rixon, F. J. & Chiu, W. (1999). Journal of Virology
Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission.
Liu, S., Xia, X., Calvo, E. & Zhou, Z. H. (2023). Nature Communications
Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase.
Ito, F., Alvarez-Cabrera, A. L., Liu, S., Yang, H., Shiriaeva, A., Zhou, Z. H. & Chen, X. S. (2023). Science Advances

The epitope arrangement on flavivirus particles contributes to Mab C10’s extraordinary neutralization breadth across Zika and dengue viruses.
Sharma, A., Zhang, X., Dejnirattisai, W., Dai, X., Gong, D., Wongwiwat, W., Duquerroy, S., Rouvinski, A., Vaney, M.-C., Guardado-Calvo, P., Haouz, A., England, P., Sun, R., Zhou, Z. H., Mongkolsapaya, J., Screaton, G. R. & Rey, F. A. (2021). Cell
Structure of active human telomerase with telomere shelterin protein TPP1.
Liu, B., He, Y., Wang, Y., Song, H., Zhou, Z. H. & Feigon, J. (2022). Nature
Structure, dynamics and assembly of the ankyrin complex on human red blood cell membrane.
Xia, X., Liu, S. & Zhou, Z. H. (2022). Nature Structural & Molecular Biology
Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150.
Yu, X., Jih, J., Jiang, J. & Zhou, Z. H. (2017). Science
Structure and mutagenesis reveal essential capsid protein interactions for KSHV replication.
Dai, X., Gong, D., Lim, H., Jih, J., Wu, T.-T., Sun, R. & Zhou, Z. H. (2018) Nature
Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome.
Liu, Y.-T., Jih, J., Dai, X., Bi, G.-Q. & Zhou, Z. H. (2019). Nature

Cryo-EM Model of the Bullet-Shaped Vesicular Stomatitis Virus.
Ge, P., Tsao, J., Schein, S., Green, T. J., Luo, M. & Zhou, Z. H. (2010). Science
Multiple conformations of trimeric spikes visualized on a non-enveloped virus.
Zhang, Y., Cui, Y., Sun, J. & Zhou, Z. H. (2022). Nature Communications
Atomic structure of the translation regulatory protein NS1 of bluetongue virus.
Kerviel, A., Ge, P., Lai, M., Jih, J., Boyce, M., Zhang, X., Zhou, Z. H. & Roy, P. (2019). Nature Microbiology

Research & Facilities 

Zhou Lab
California Nanosystems Institute (CNSI)
University of California Los Angeles (UCLA)
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