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Ping Zhu, Ph.D, Prof.
National Laboratory of Biomacromolecules, IBP
3D reconstruction and structural analysis of virus, macrobiomolecules and complexes by cryoEM
Chinese personal homepage
Biography & Introduction
1986.9-1990.6 Bachelor, Zhejiang Univ., Hangzhou, China
1990.9-1993.6 Master, Xi’an Jiaotong Univ., Xi’an, China
1993.9-1997.6 Ph.D., Tsinghua Univ., Beijing, China
1997.7-1998.12 Lecturer, Tsinghua Univ., Beijing, China
1999.3-2008.5 Postdoctoral Research Associate; Assist. in Research (NTTF) ; Associate Scholar/Scientist (NTTF); Florida State Univ., Tallahassee, Florida, USA
2008.6-present Principal Investigator, Professor of “Hundred Talents Program”, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
Our lab is interested in the 3D reconstruction and structural analysis of virus, macrobiomolecules and complexes utilizing cryo electron microscopy (cryoEM) and cryo electron tomography (cryoET). Rapidly developed in the past decades, cryo electron microscopy provides a unique way to study the 3D structure of macrobiomolecules in their native status.
(1) The structure feature of envelope glycoproteins (ENV) on the surface of AIDS viruses
Envelope glycoproteins, namely gp120 and gp41, play critical role during the entry process of HIV-1 virus into the target cell and serve as the most obvious AIDS vaccine candidate. We initiated the analysis of the 3-D surface feature of AIDS virus by electron tomography (Zhu et al., PNAS , 2003) and reported the first 3-D images of the envelope spike on SIV surface (Zhu et al., Nature, 2006, article). We also discovered a distinct VH domain swapped structure of 2G12, one of the few identified HIV-1 widely neutralizing antibodies (Calarese et al, Science, 2003, research article). As an ongoing project in the lab, we are working on improving our knowledge on the 3-D structure of HIV-1 surface proteins by cryoEM and cryoET, both alone and in complexes with key receptors and neutralizing antibodies (Zhu et al., PLoS Pathog., 2008). To provide insights into the rational AIDS vaccine design, we are also interested in the electron microscopic analysis of reconstituted soluble HIV-1 ENV trimer (Kang et al, Vaccine, 2009), and the enveloped HIV virus-like particles (VLPs) (Yang et al, J. Virol., 2012), as HIV-1 vaccine candidates.
(2) 3D reconstruction of virus at near-atomic resolution by cryoEM
The relatively low resolution (typically around ~10-20?) of cryoEM reconstruction compared with x-ray crystallography prevents researchers from getting the detailed information about the assembly of virus and other molecular machines at the molecular level. Taking advantage of the state-of-the-art 300KV Titan Krios FEG transmission cryo electron microscope recently installed in the Institute of Biophysics, we reconstructed the 3D structure of a cypovirus (CPV) from Reoviridae at near-atomic resolution (3.9 Å) using cryoEM single particle analysis, and built a full atomic model of this virus (Cheng et al, PNAS, 2011). This work provides significant insights into the mRNA capping mechanism of dsRNA viruses, and represents the first full atomic model (with amino acid side chains) built exclusively from 4kx4k CCD image data.
Most recently, we have reconstructed the 3D structure of the same cypovirus (CPV) in its transcribing state at near-atomic resolution, and built an atomic structural model of this transcribing dsRNA virus (Yang et al, PNAS, 2012). This work revealed the structural changes of the capsid proteins that are associated with dsRNA virus transcription, and provided structural evidence to the hypothesis of mRNA release channel in the dsRNA virus capsid shell. A highly coordinated transcription and mRNA capping process of dsRNA virus was revealed. It also represents the first atomic structure of transcribing virus.
(3) Structure basis of 30nm chromatin and chromatin remodeling
Although the nucleosomes have widely been thought to be folded into 30nm chromatin fibres, how the chromatin fibres are organized and reshaped by “chromatin remodelers” remains elusive. CryoEM and electron tomography provides the most suitable tools to study the higher-order structure of 30nm chromatin. We are interested in the 3D structural analysis of 30nm chromatin and how they are modified by chromatin remodeling complexes, using cryo electron microscopy and electron tomography techniques.
We are also interested in the 3-D structure and function of other significant molecules, viruses, cells and their complexes, as well as visualizing the important biological processes, for example, the entry of virus into the target cell.
1. Cheng L., Sun J., Zhang K., Mou Z., Huang X., Ji G., Sun F., Zhang J.*, Zhu P.* (2011) Atomic model of a cypovirus built from cryo-EM structure provides insight into the mechanism of mRNA capping. Proc. Natl. Acad. Soc. USA, 108:1373–1378
2. Yang C., Ji G., Liu H., Zhang K., Liu G., Sun F., Zhu P.*, Cheng L.* (2012) Cryo-EM Structure of a transcribing cypovirus. Proc. Natl. Acad. Soc. USA,109:6118-23
3. Zhu P., Winkler H., Chertova E., Taylor K., Roux K. (2008) Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs. PLoS Pathog. 4(11): e1000203.
4. Yang L., Song Y., Li X., Huang X., Liu J., Ding H., Zhu P., Zhou P. (2012) HIV-1 Virus Like Particles Produced by Stably Transfected Drosophila S2 cells - a Desirable Vaccine Component. J. Virol., 86(14):7662-7676 (recommended by Faculty of 1000)
5. 黄晓星，宋晓伟，朱平*. (2010) 冷冻电子断层成像技术及其在生物研究领域的应用. 生物物理学报. 26 (7): 209-215 (invited review)
List of publications (in chronological order):
1. Yang C, Ji G, Liu H, Zhang K, Liu G, Sun F, Zhu P*, Cheng L*. (2012) Cryo-EM Structure of a transcribing cypovirus. Proc. Natl. Acad. Soc. USA,109:6118-23
2. Yang L, Song Y, Li X, Huang X, Liu J, Ding H, Zhu P, Zhou P. (2012) HIV-1 Virus Like Particles Produced by Stably Transfected Drosophila S2 cells - a Desirable Vaccine Component. J. Virol., 86(14):7662-7676 (recommended by Faculty of 1000)
3. Rathinakumar R, Dutta M, Zhu P, Johnson W, Roux K. (2012) Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions. J. Virol., 86(3):1820-31
4. Cheng L, Sun J, Zhang K, Mou Z, Huang X, Ji G, Sun F, Zhang J*, Zhu P*. (2011) Atomic model of a cypovirus built from cryo-EM structure provides insight into the mechanism of mRNA capping. Proc. Natl. Acad. Soc. USA, 108:1373–1378
5. 朱平. (2011) “电子断层成像技术与病毒研究”, book chapter in “病毒的电子显微学研究”. 张景强 主编. 科学出版社. ISBN 978-7-03-31579-3, pp209-219
6. 黄晓星，宋晓伟，朱平*. (2010) 冷冻电子断层成像技术及其在生物研究领域的应用. 生物物理学报. 26 (7): 209-215 (invited review)
7. Kang Y, Andjelic S, Binley J, Crooks E, Franti M, Iyer S, Donovan G, Dey A, Zhu P, Roux K, Durso R, Parsons T, Maddon P, Moore J, Olson W. (2009) Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1. Vaccine. 27: 5120–5132
8. Winkler H, Zhu P, Liu J, Ye F, Roux K, Taylor K. (2009) Tomographic subvolume alignment and subvolume classification applied to myosinV and SIV envelope spikes. J. Struc. Biol.,165:64-77
9. Zhu P, Winkler H, Chertova E, Taylor K, Roux K. (2008) Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs. PLoS Pathog. 4(11): e1000203.
10. Selvarajah S, Puffer B, Lee F, Zhu P, Li Y, Wyatt R, Roux K, Doms R, Burton D. (2008) Focused Dampening of Antibody Response to the Immunodominant Variable Loops by Engineered Soluble gp140. AIDS Res. Human Retroviro. 24:301-14
11. Crooks E, Moore P, Franti M, Cayanan C, Zhu P, Jiang P, de Vries R, Wiley C, Zharkikh I, Schulke N, Roux K, Montefiori D, Burton D, Binley J. (2007) A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and soluble monomeric gp120. Virology. 366:245-262 (cover)
12. Roux K, Taylor K, Zhu P. (2006) Cryoelectron Tomography Shows 3D Structure of Surface Spikes – Structure of AIDS Virus Surface Revealed. BIOforum Europe. 7/8:32-3 ( invited communication review)
13. Zhu P, Liu J, Bess J., Chertova E, Lifson J, Grisé H, Ofek G, Taylor K, Roux K. (2006) Distribution and Three-Dimensional Structure of AIDS Virus Envelope Spikes. Nature. 441:847-852 (Article)
14. Moore P, Crooks E, Porter L, Zhu P, Cayanan C, Grise H, Corcoran P, Zwick M, Franti M, Morris L, Roux K, Burton D, Binley J. (2006) Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol. 80: 2515-28
15. Pancera M, Lebowitz J, Schon A, Zhu P, Freire E, Kwong P, Freire E, Roux K, Sodroski J, Wyatt R. (2005) Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol. 79: 9954-69
16. Roux KH, Zhu P, Seavy M, Katinger H, Kunert R, Vest VS. (2004) Electron microscopic and Immunochemical analysis of the broadly neutralizing HIV-1-specific, anti-carbohydrate antibody, 2G12. Mol. Immunol., 41:1001-11
17. L?set GA, Roux KH, Zhu P, Michaelsen TE, and Sandlie I. (2004) Differential Segmental Flexibility and Reach Dictate the Antigen Binding Mode of Chimeric IgD and IgM: Implications for the Function of the B Cell Receptor. J. Immunol. 172: 2925-34
18. Zhu P, Chertova E., Bess J, Lifson J, Arthur L, Liu J, Taylor KA, Roux KH. (2003) Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc. Natl. Acad. Soc. USA, 100:15812-15817
19. Srivastava I, Stamatatos L, Kan E, Martin L, Vita C, Zhu P, Roux KH, Vojtech L, Lian Y, Hilt S, Ulmer JB, Barnett SW. (2003) Purification, Characterization, and Immunogenicity of a Soluble Trimeric Envelope Protein Containing a Partial Deletion of the V2 Loop Derived from SF162, an R5-Tropic Human Immunodeficiency Virus Type 1 Isolate. J. Virol. 77: 11244-59
20. Calarese DA, Scanlan CN, Zwick MB, Deechongkit S, Mimura Y, Kunert R, Zhu P, Wormald, MR, Stanfield RL, Roux KH, Kelly JW, Rudd PM, Dwek RA, Katinger H, Burton DR, Wilson IA. (2003) Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science. 300:2065-71 (Research Article)
21. Schülke N, Vesanen MS, Sanders RW, Zhu P, Lu M, Anselma DJ, Villa AR, Parren PW, Binley JM, Roux KH, Maddon PJ, Moore JP, Olson W. (2002) Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76:7760-7766.
22. Zhu P, Olson WC, Roux KH. (2001) Structural Flexibility and Function Valency of CD4-IgG2 (PRO 542): Potential for Crosslinking HIV-1 Envelope Spikes, J Virol., 75:6682-6686.
From Ping Zhu, 2014-01-08 update