Ph.D., Professor, “Hundred Talents Program” , CAS
Our research interest is to understand the mechanism of chaperone-assisted protein folding and disaggregation by using electron cryomicroscopy (cryo-EM) single particle and cryotomography techniques, in combination with bioinformatics and flexible fitting tools.
Defects in protein folding are associated with a wide variety of human diseases, including cancer and aggregation-linked neurodegenerative diseases such as Huntington’s, Parkinson’s, and Alzheimer’s diseases. Chaperone is a class of proteins which can assist protein folding correctly in the cell. There is a group of oligomeric double-ring chaperones called chaperonin. The eukaryotic chaperonin TRiC/CCT folds ~5-10% of cytosolic proteins including many key structural and regulatory proteins, many of which cannot be folded by any other chaperone. However, little is known about this protein folding nanomachine due to its structural complexity. We focus on the structural mechanisms of how chaperone, such as TRiC/CCT, recognizes its substrate, and how ATP binding and hydrolysis drive its conformational changes and lead to a productive substrate folding. In the long-run, we will extend our study to comprehend how the critical chaperone and its cochaperone cooperate together to assist the protein folding and disaggregation.
Another research interest is the image alignment method and modeling tool development and application in cryo-EM data analysis. We have developed a novel FRM2D method for accurate and efficient 2D image alignment in single particle analysis, which has been successfully applied in resolving several subnanometer resolution cryo-EM structures and is available to the fields through EMAN software package.
1. Guo, X., Wang, L., Li, J., Ding, Z., Xiao, J., Yin, X., He, S., Shi, P., Dong, L., Li, G., Tian, C., Wang, J., Cong, Y., and Xu, Y.*(2014). Structural Insight into Autoinhibition and Histone H3-induced Activation of DNMT3A, Nature. (accepted)
2. Ye, X., Ku, Z., Liu, Q., Wang, X., Shi, J., Zhang, Y., Kong, L., Cong, Y., Huang, Z. (2014). Chimeric virus-like particle vaccines displaying conservedenterovirus 71epitopes elicit protective neutralizing antibodies in mice through divergentmechanisms. Journal of Virology. 88:72-81.
3. Shahmoradian, S. H., Galaz-Montoya, J. G., Schmid, M. F., Cong, Y., Ma, B., Spiess, C., Frydman, J., Ludtke, S. J., Chiu, W. (2013). TRiC＇s tricks inhibit huntingtin aggregation. eLife. 2:e00710.
4. Zhang, Q., Dai, X., Cong, Y., Zhang, J., Chen, D., Dougherty, M. T., Wang, J., Ludtke, S. J., Schmid, M. F., Chiu, W.(2013). Cryo-EM Structure of a Molluscan Hemocyanin Suggests Its Allosteric Mechanism. Structure. 21:604-613.
5. Feng, M., Ding, Z., Xu, L., Kong, L., Wang, W., Jiao, S., Shi, Z., Greene, M.I., Cong, Y.*, Zhou, Z.* (2013). Structural and biochemical studies of RIG-I antiviral signaling. Protein Cell. 4(2):142-54.
6. Leitner, A., Joachimiak, L.A., Bracher, A., Monkemeyer, L., Walzthoeni, T., Chen, B., Pechmann, S., Holmes, S., Cong, Y., Ma, B., Ludtke, S., Chiu, W., Hartl, F.U., Aebersold, R., Frydman, J. (2012). The molecular architecture of the eukaryotic chaperonin TRiC/CCT. Structure. 20, 814-825.
7. Cong, Y., Schroder, G.F., Meyer, A.S., Jakana, J., Ma, B., Dougherty, M.T., Schmid, M.F., Reissmann, S., Levitt, M., Ludtke, S.L., Frydman, J., Chiu, W. (2012). Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle. EMBO Journal. 31, 720-730.
8. Zhang, R., Hryc, C.F., Cong, Y., Liu, X., Jakana, J., Gorchakov, R., Baker, M.L., Weaver, S.C., Chiu, W. (2011), 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO Journal. 30, 3854-3863.
9. Cong, Y., Ludtke, S.L. (2010). Single Particle Analysis at High Resolution. Methods in Enzymology. 482, 211-235.
10. Cong, Y., Baker, M.L., Jakana, J., Woolford, D., Miller, E.J., Reissmann, S., Kumar, R.N., Redding-Johanson, A.M., Batth, T.S., Mukhopadhyay, A., Ludtke, S.L., Frydman, J., Chiu, W. (2010). 4.0 Å Resolution Cryo-EM Structure of the Mammalian Chaperonin TRiC/CCT Reveals its Unique Subunit Arrangement. Proc Natl Acad Sci. 107, 4967-4972. [F1000 Factor 8 (Must Read) by Faculty of 1000 Biology]
11. Cong, Y., Zhang, Q., Woolford, D., Schweikardt, T., Khant, H., Dougherty, M., Ludtke, S.J., Chiu, W., Decker, H. (2009). Structural Mechanism of SDS-induced Enzyme Activity of Scorpion Hemocyanin Revealed by Electron Cryo-Microscopy. Structure. 17, 749-758. [Reported by more than 10 American and German scientific websites including Science Daily, Medical News Today, C&EN, etc.]
12. Booth, C.R., Meyer, A.S., Cong, Y., Topf, M., Sali, A., Ludtke, S.J., Chiu, W., and Frydman, J. (2008). Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nat Struct Mol Biol. 15, 746-753.
13. Cong, Y., Topf, M., Sali, A., Matsudaira, P., Dougherty, M., Chiu, W., and Schmid, M.F. (2008). Crystallographic conformers of actin in a biologically active bundle of filaments. J Mol Biol. 375, 331-336. [F1000 Factor 8 (Must Read) by Faculty of 1000 Biology]
14. Serysheva, I.I., Ludtke, S.J., Baker, M.L., Cong, Y., Topf, M., Eramian, D., Sali, A., Hamilton, S.L., and Chiu, W. (2008). Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel. Proc Natl Acad Sci. 105, 9610-9615
15. Cong, Y., Jiang, W., Birmanns, S., Zhou, Z.H., Chiu, W., and Wriggers, W. (2005). Fast rotational matching of single-particle images. J Struct Biol. 152, 104-112.
16. Cong, Y., Kovacs, J.A., and Wriggers, W. (2003). 2D fast rotational matching for image processing of biophysical data. J Struct Biol. 144, 51-60.
17. Kovacs, J.A., Chacon, P., Cong, Y., Metwally, E., and Wriggers, W. (2003). Fast rotational matching of rigid bodies by fast Fourier transform acceleration of five degrees of freedom. Acta Crystallogr D Biol Crystallogr. 59, 1371-1376.
18. Yang, Z.Z., Cong, Y., Zhao, D.X., Wang, C.S., and Bao, X.H. (2003). Sigma Pi Scheme in Atom-Bond Electronegativity Equalization Method. J Chin Chem Soc-Taipei. 50, 785-794.
19. Cong, Y., Yang, Z.Z., Wang, C.S., Liu, X.C., and Bao, X.H. (2002). Investigation of the regio- and stereo-selectivity of Diels-Alder reactions by the newly developed ABEEMσπ model on the basis of local HSAB principle and maximum hardness principle. Chem Phys Lett. 357, 59-64.
20. Cong, Y., and Yang, Z.Z. (2000). General atom-bond electronegativity equalization method and its application in prediction of charge distributions in polypeptide. Chem Phys Lett. 316, 324-329.
21. Niu, S.Y., Jin, J., Jin, X.L., Cong, Y., and Yang, Z.Z. (2000). Crystal structure and magnetism of the binuclear Gd(III) complex Gd2(C12H8N2)2(C6H5COO)6. Chin Sci Bull. 45, 706-711.
22. Yang, Z.Z., Cong, Y., and Wang, C.S. (1999). Sigma pi model in the atom-bond electronegativity equalization method and its applications. Chem J Chin Univ. 20, 1781-1783. (in Chinese)
23. Li, S.M., Wang, M.L., Cong, Y., and Yang, Z.Z. (1998). Energy transfer of Excited Normal Modes in H2X(X=O,S). Chem J Chin Univ. 19, 950-954. (in Chinese)
24. Wang, C.S., Sun, R.A., Cong, Y., and Yang, Z.Z. (1997). A Theoretical Study of PdCONaOH Complex as a Sample Model of Promoted Catalysis. J Inorg Chem.13, 301-305. (in Chinese)
Education Background & Academic Experience
2011.7-present: Principle Investigator, Institute of Biochemistry and Cell Biology, SIBS, CAS
2010.10-2011.7: Instructor, National Center for Macromolecular Imaging, Baylor College of Medicine, TX
2005.6-2010.9: Research Associate, National Center for Macromolecular Imaging, Baylor College of Medicine, TX.
2001.11-2005.5: Postdoctoral Associate, Laboratory of Dr. Willy Wriggers, The Scripps Research Institute, CA; University of Texas Health Science Center at Houston, TX.
2000.9-2001.10: Postdoctoral Research, Dalian Institute of Chemical Physics, CAS, China
1995.9-2000.6: Ph.D. in Physical Chemistry, Jilin University, Jilin, China.
1991.9-1995.7: B.S. in Chemistry, Liaoning Normal University, Liaoning, China.