Home CAS Center for Excellence


Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: cong@@sibcb.ac.cn

Research Interests
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.

Selected Publications

  1. Yin W, Li Z, Jin M, Yin YL, Waal PW, Pal K, Yin Y, Gao X, He Y, Gao J, Wang X, Zhang Y, Zhou H, Melcher K, Jiang Y, Cong Y*, Zhou XE*, Yu X*, Xu HE*. (2019) A complex structure of arrestin-2 bound to a G protein-coupled receptor. Cell Research, 29:971每983.
  2. Jin M, Han W, Liu C, Zang Y, Li J, Wang F, Wang Y, Cong Y*. (2019) An ensemble of cryo-EM structures of TRiC reveals its conformational landscape and subunit specificity. Proc Natl Acad Sci, 116(39):19513每19522.
  3. Ding Z, Xu C, Sahu I, Wang Y, Fu Z, Huang M, Wong CCL, Glickman MH, and Cong Y*. (2019) Structural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations. Molecular Cell, 73:1-12.
  4. Chen J, Ye X, Zhang X, Zhu Z, Zhang X, Xu Z, Ding Z, Zou G, Liu Q, Kong L, Jiang W, Zhu W, Cong Y*and Huang Z*. (2019) Coxsackievirus A10 atomic structure facilitating the discovery of a broadspectrum inhibitor against human enteroviruses. Cell Discovery, 5:4.
  5. Wang Y, Ding Z, Liu X, Bao Y, Huang M, Wong CCL, Hong X, Cong Y*. (2018) Architecture and subunit arrangement of the complete Saccharomyces cerevisiae COMPASS complex. Scientific Reports, 8:17405.
  6. Wang H, Han W, Takagi J*, Cong Y*. (2018) Yeast inner-subunit PA每NZ-1 labeling strategy for accurate subunit identification in a macromolecular complex through cryo-EM analysis. Journal of Molecular Biology,430(10):1417-1425.
  7. Zang Y, Wang H, Cui Z, Jin M, Liu C, Han W, Wang YX, Cong Y*. (2018) Development of a yeast internal-subunit eGFP labeling strategy and its application in subunit identification in eukaryotic group II chaperonin TRiC/CCT. Scientific Reports, 8(1):2374.
  8. Chen J, Zhang C, Zhou Y, Zhang X, Shen C, Ye X, Jiang W, Huang Z* and Cong Y*.  (2018) A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. Journal of Virology, 92: e01257-17
  9. Wang X, Ku Z, Zhang X, Ye X, Chen J, Liu Q, Zhang W, Zhang C, Fu Z, Jin X, Cong Y* and Huang Z*. (2018) Structure, Immunogenicity and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid. Journal of Virology, 92:e01330-17.
  10. Jin M, Cong Y. (2017) Identification of an allosteric network that influences assembly and function of group II chaperonins. Nat Struct Mol Biol, 24:683每684.
  11. Fan C, Ye X, Ku Z, Kong L, Liu Q, Xu C, Cong Y*, Huang Z*. (2017) Beta-propiolactone inactivation of coxsackievirus A16 induces structural alteration and surface modification of viral capsids.Journal of Virology, 91:e00038-17.
  12. Ding Z, Fu Z, Xu C, Wang YF, Wang YX, Li J, Kong L, Chen J, Li N, Zhang R, Cong Y*. (2017) High-resolution cryo-EM structure of the proteasome in complex with ADP-AlFx. Cell Research, 27:373每385.
  13. Zang Y, Jin M, Wang H, Cui Z, Liu C, Kong L, Cong Y*. (2016) Staggered ATP-binding mechanism of eukaryotic chaperonin TRiC/CCT revealed by high-resolution cryo-EM. Nat Struct Mol Biol, 23(12):1083-1091.
  14. Shao J, Fu Z, Ji Y, Guan X, Guo S, Ding Z, Yang X*, Cong Y*, Shen Y*. (2016) Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter. Scientific Reports, 6:34174.
  15. Ye X, Fan C, Ku Z, Zuo T, Kong L, Zhang C, Shi J, Liu Q, Chen T, Zhang Y, Jiang W, Zhang L, Huang Z*, Cong Y*. (2016) Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody. PLoS Pathogens, 12(3):e1005454.
  16. Oxenoid K, Dong Y, Cao C, Cui T, Sancak Y, Markhard AL, Grabarek Z, Kong L, Liu Z, Ouyang B, Cong Y, Mootha VK, Chou JJ*. (2016) Architecture of the mitochondrial calcium uniporter. Nature, 533(7602):269-273.
  17. Jin W, Wang Y, Liu CP, Yang N, Jin M, Cong Y, Wang M*, Xu RM*. (2016) Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5. Genes & Dev, 30(21):2391-2403.
  18. Cheng H, Fan C, Zhang S, Wu Z, Cui Z, Melcher K, Zhang C, Jiang Y, Cong Y, Xu HE*. (2015) Crystallization scale purification of a7 nicotinic acetylcholine receptor from mammalian cells using a BacMam expression system. Acta Pharmacol Sin, 36(8):1013-1023.
  19. Wu Z, Cui Z, Cheng H, Fan C, Melcher K, Jiang Y, Zhang C, Jiang H, Cong Y, Liu Q*, Xu HE*. (2015) High yield and efficient expression and purification of the human 5-HT3A receptor. Acta Pharmacol Sin, 36(8):1024-1032.
  20. 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, Xu Y*. (2015) Structural Insight into Autoinhibition and Histone H3-induced Activation of DNMT3A. Nature, 517(7536):640-644.
  21. 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(1):72-81.
  22. Shahmoradian SH, Galaz-Montoya JG, Schmid MF, Cong Y, Ma B, Spiess C, Frydman J, Ludtke SJ, Chiu W*. (2013) TRiC*s tricks inhibit huntingtin aggregation. eLife, 2:e00710.
  23. Zhang Q, Dai X, Cong Y, Zhang J, Chen DH, Dougherty MT, Wang J, Ludtke SJ, Schmid MF, Chiu W*. (2013) Cryo-EM Structure of a Molluscan Hemocyanin Suggests Its Allosteric Mechanism. Structure, 21(4):604-613.
  24. Feng M, Ding Z, Xu L, Kong L, Wang W, Jiao S, Shi Z, Greene MI, Cong Y*, Zhou Z*. (2013) Structural and biochemical studies of RIG-I antiviral signaling. Protein Cell, 4(2):142-154.
  25. Leitner A, Joachimiak LA, Bracher A, Mönkemeyer L, Walzthoeni T, Chen B, Pechmann S, Holmes S, Cong Y, Ma B, Ludtke S, Chiu W, Hartl FU, Aebersold R*, Frydman J*. (2012) The Molecular Architecture of the Eukaryotic Chaperonin TRiC/CCT. Structure, 20(5):814-825.
  26. Cong Y, Schröder GF, Meyer AS, Jakana J, Ma B, Dougherty MT, Schmid MF, Reissmann S, Levitt M, Ludtke SL, Frydman J, Chiu W*. (2012) Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle. EMBO Journal, 31(3):720-730.
  27. Zhang R, Hryc CF, Cong Y, Liu X, Jakana J, Gorchakov R, Baker ML, Weaver SC, Chiu W*. (2011) 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO Journal, 30(18):3854-3863.
  28. Cong Y, Ludtke SL. (2010) Single Particle Analysis at High Resolution. Methods in Enzymology, 482:211-235.
  29. Cong Y, Baker ML, Jakana J, Woolford D, Miller EJ, Reissmann S, Kumar RN, Redding-Johanson AM, Batth TS, Mukhopadhyay A, Ludtke SJ, 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(11):4967-4972.
  30. Cong Y, Zhang Q, Woolford D, Schweikardt T, Khant H, Dougherty M, Ludtke SJ, Chiu W*, Decker H*. (2009) Structural Mechanism of SDS-induced Enzyme Activity of Scorpion Hemocyanin Revealed by Electron Cryo-Microscopy. Structure, 17(5):749-758.
  31. Booth CR, Meyer AS, Cong Y, Topf M, Sali A, Ludtke SJ, Chiu W*, Frydman J*. (2008) Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nat Struct Mol Biol, 15(7):746-753.
  32. Cong Y, Topf M, Sali A, Matsudaira P, Dougherty M, Chiu W, Schmid MF*. (2008) Crystallographic conformers of actin in a biologically active bundle of filaments. J Mol Biol, 375(2):331-336.
  33. Serysheva II, Ludtke SJ, Baker ML, Cong Y, Topf M, Eramian D, Sali A, Hamilton SL, Chiu W*. (2008) Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel. Proc Natl Acad Sci, 105(28):9610-9615.
  34. Cong Y, Jiang W, Birmanns S, Zhou ZH, Chiu W, Wriggers W *. (2005) Fast rotational matching of single-particle images. J Struct Biol, 152(2):104-112.
  35. Cong Y, Kovacs JA, Wriggers W. (2003) 2D fast rotational matching for image processing of biophysical data. J Struct Biol, 144(1-2):51-60.
  36. Kovacs JA, Chac車n P, Cong Y, Metwally E, 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(8):1371-1376.
  37. Yang Z*, Cong Y, Zhao D, Wang C, Bao XH. (2003) Sigma Pi Scheme in Atom-Bond Electronegativity Equalization Method. J Chin Chem Soc-Taipei, 50:785-794.
  38. Sun R*, Liu Y, Sun Y, Cong Y, Zhang Z. (2003) Theoretical studies of Si6H3 Si5H6 Si5Li3 and Si5Na3 cluster. J Mol Sci, 19:103-108.
  39. Cong Y*, Yang Z, Wang C, Liu X, Bao X. (2002) Investigation of the regio- and stereo-selectivity of Diels-Alder reactions by the newly developed ABEEM考羽 model on the basis of local HSAB principle and maximum hardness principle. Chem Phys Lett, 357:59-64.
  40. Cong Y, Yang Z. (2000) General atom-bond electronegativity equalization method and its application in prediction of charge distributions in polypeptide. Chem Phys Lett, 316:324-329.
  41. Niu S, Jin J, Jin X, Cong Y, Yang Z*. (2000) Crystal structure and magnetism of the binuclear Gd(III) complex Gd2(C12H8N2)2(C6H5COO)6. Chin Sci Bull, 45(8):706-711.
  42. Yang Z*, Cong Y, Wang C. (1999) Sigma pi model in the atom-bond electronegativity equalization method and its applications. Chem J Chin Univ, 20:1781-1783.
  43. Li S, Wang M, Cong Y, Yang Z*. (1998) Energy transfer of Excited Normal Modes in H2X(X=OS). Chem J Chin Univ, 19:950-954.
  44. Wang C, Sun R, Cong Y, Yang Z. (1997) A Theoretical Study of PdCONaOH Complex as a Sample Model of Promoted Catalysis. J Inorg Chem, 13:301-305. 

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.

Research Team

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