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  • 丛尧
  • 研究员，研究组长，博士生导师
  • E-mail: cong@@sibcb.ac.cn
  • 实验室主页: 
    个人简介：

  • 　　1995年7月辽宁师范大学获学士学位;2000年7月吉林大学获博士学位。2000年9月至2001年10月，在中科院大连化学物理研究所从事博士后研究工作。2001年11月至2005年5月，先后在美国Scripps研究所及德州大学休斯顿健康信息中心的Willy Wriggers研究组任博士后。其中2004年1月至2005年12月获美国W. M. Keck 基金会Postdoctoral Fellowship资助。2005年6月至2011年7月，美国Baylor College of Medicine，先后任Research Associate, Instructor。2011年7月起，任中科院上海生科院生化与细胞所研究员、博士生导师。获国家基金委“优秀青年”(2013年)基金资助。

    社会任职：
    研究方向：
  • 蛋白质质量控制大分子机器的结构与功能
    研究工作：

  • 　　本研究组致力于解析分子伴侣协助下的蛋白质折叠与解聚的机理。主要实验手段包括超低温冷冻电镜(cryo-EM)单颗粒重组以及低温电子断层扫描技术(cryo-Electron Tomography)，并结合生物信息学和分子柔性装配等计算工具。

    　　蛋白质折叠中的缺陷通常伴随着许多人类疾病，包括癌症及蛋白聚集引起的神经退行性疾病，如帕金森氏综合症和亨廷顿舞蹈病等。分子伴侣(chaperone)是一类可以协助细胞中蛋白质正确折叠的分子机器，其中真核细胞中双环背对背堆叠的多聚体分子伴侣素(chaperonin)TRiC/CCT是最为复杂的分子伴侣。它可以帮助~5-10%胞质蛋白的折叠，包括许多重要的结构和调节蛋白。然而，由于其结构的复杂性导致对此重要分子机器的结构知之甚少。我们的研究兴趣在于解析分子伴侣如TRiC是如何识别并结合它的底物，三磷酸腺苷(ATP)触发下其构象变化与底物蛋白正确折叠之间的相互关系。长期着眼，我们会进一步研究重要分子伴侣极其cochaperone之间如何相互作用来共同协助底物蛋白质的折叠与解聚。

    　　我们的另外一个研究方向是二维图像对位(image alignment)方法及分子柔性装配(flexible fitting)工具的发展及其在cryo-EM数据处理中的应用。我们发展了创新性的二维快速转动匹配方法，简称FRM2D。该方法不仅计算精度高于传统方法并且极大缩减了计算时间。此方法已成功应用于十余个中、高分辨率大分子复合物结构的三维重组过程中。此外，FRM2D方法已被嵌入冷冻电镜领域三大应用最广泛的单颗粒重组软件包之一EMAN之中，供其在世界范围内的用户免费使用。

    承担科研项目情况：
    代表论著：
    1. Meng X, Xu C, Li J, Qiu B, Luo J, Hong Q, Tong Y, Fang C, Feng Y, Ma R, Shi X, Lin C, Pan C, Zhu X*, Yan X*, Cong Y*. (2024) Multi-scale structures of the mammalian radial spoke and divergence of axonemal complexes in ependymal cilia. Nat Commun, 15:362.
    2. Diao L, Zheng W, Zhao Q, Liu M, Fu Z, Zhang X, Bao L*, Cong Y* .(2023) Cryo-EM of α-tubulin isotype-containing microtubules revealed a contracted structure of α4A/β2A microtubules. ABBS, 55(11):1-10.
    3. Xu C, Han W, Cong Y*. (2023) Cryo-EM and cryo-ET of the spike, virion, and antibody neutralization of SARS-CoV-2 and VOCs. Current Opinion in Structural Biology, 82:102664.
    4. Liu C, Jin M, Wang S, Han W, Zhao Q, Wang YF, Xu C, Diao L, Yin Y, Peng C, Bao L, Wang YX, Cong Y*. (2023) Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM . Commun Biol, 6(1): 1-14.
    5. He L, Zhao Q, Qi J, Wang Y, Han W, Chen Z, Cong Y*, Wang S*. (2023) Structural insights into constitutive activity of 5-HT6 receptor. Proc Natl Acad Sci, 120(14): e2209917120.
    6. Han W, Jin M, Liu C, Zhao Q, Wang S, Wang YF, Yin Y, Peng C, Wang YX, Cong Y*. (2023) Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT. Sci Adv, 9(11): eade1207.
    7. Zhang C, Liu C, Shi J, Wang Y, Xu C, Ye X, Liu Q, Li X, Qiao W, Yin Y, Cong Y*, Huang Z*. (2022) Molecular mechanism of antibody neutralization of coxsackievirus A16. Nat Commun,13:7854.
    8. Sun X, Liu C, Lu X, Ling Z*, Yi C, Zhang Z, Li Z, Jin M, Wang W, Tang S, Wang FF, Wang F,Wangmo S, Chen S, Li L, Ma L, Zhang Y, Yang Z, Dong X, Qian Z, Ding J, Wang D*, Cong Y*, Sun B*. (2022) Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus. Nat Commun,13:2378.
    9. Hong Q, Han W, Li J, Xu S, Wang YF, Xu C, Li Z, Wang YX*, Zhang C*, Huang Z*, Cong Y*. (2022) Molecular basis of receptor binding and antibody neutralization of Omicron. Nature, 604:546–552.
    10. Wang YF, Liu C, Zhang C, Wang YX, Hong Q, Xu S; Li Z, Yang Y, Huang Z*, Cong Y*. (2022) Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies. Nat Commun, 13:871.
    11. Xu S, Wang YF, Wang YX, Zhang C, Hong Q, Gu C, Xu R, Wang T, Yang Y, Zang J, Zhou Y, Li Z, Liu Q, Zhou B, Bai L, Zhu Y, Deng Q, Wang H, Lavillette D, Wong G*, Xie Y*, Cong Y*, Huang Z*. (2022) Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein. Emerging Microbes & Infections, 11（1）:351-367.
    12. Wang YF, Xu C, Wang YX, Hong Q, Zhang C, Li Z, Xu S, Zuo Q, Liu C, Huang Z*, Cong Y*. (2021) Conformational dynamics of the Beta and Kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM. Nat Commun, 12:7345.
    13. Wang N, Wang Y, Zhao Q, Zhang X, Peng C, Zhang W, Liu Y, Vallon O, Schroda M, Cong Y*, Liu C*. (2021) The cryo-EM structure of the chloroplast ClpP complex. Nat Plants, 7(1):1505-1515.
    14. Sahu I, Mali S.M., Sulkshane P, Xu C, Rozenberg A, Morag R, Sahoo M.P., Singh S.K., Ding Z, Wang Y, Day S, Cong Y, Kleifeld O*, Brik A*, Glickman M.H*. (2021) The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag. Nat Commun, 12:6173.
    15. Luo Y, Wan G, Zhou X, Wang Q, Zhang Y, Bao J, Cong Y, Zhao Y*, Li D*. (2021) Architecture of Dispatched, a Transmembrane Protein Responsible for Hedgehog Release. Front Mol Biosci, 8:701826.
    16. Li T, Cai H, Yao H, Zhou B, Zhang N, van Vlissingen MF, Kuiken T, Han W, GeurtsvanKessel CH, Gong Y, Zhao Y, Shen Q, Qin, W, Tian X, Peng C, Lai Y, Wang YX, Hutter CAJ, Kuo S-M, Bao J, Liu C, Wang YF, Richard AS, Raoul H, Lan J, Seeger MA, Cong Y, Rockx B, Wong G*, Bi Y*, Lavillette D*, Li D*.(2021) A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection. Nat Commun, 12:4635.
    17. Luo Y, Wan G, Zhang X, Zhou X, Wang Q, Fan J, Cai H, Ma L, Wu H, Qu Q*, Cong Y*, Zhao Y*, Li D*. (2021) Cryo-EM study of Patched in lipid nanodisc suggests a structural basis for its clustering in caveolae. Structure, 29(11):1286-1294.
    18. Zhang C, Xu C, Dai W, Wang Y, Liu Z, Zhang X, Wang X, Wang H, Gong S*, Cong Y*, Huang Z*.(2021) Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections. Nat Commun, 12:2904.
    19. Chen J, Wang Y, Xu C, Chen K, Zhao Q, Wang S, Yin Y, Peng C*, Ding Z*, Cong Y*.(2021) Cryo-EM of mammalian PA28αβ-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ. Nat Commun,12:739.
    20. Zheng W, Li F, Ding Z, Liu H, Zhu L, Xu C, Li J, Gao Q,Wang Y, Fu Z, Peng C, Yan X*, Zhu X*, and Cong Y*.(2021) Distinct architecture and composition of mouse axonemal radial spoke head revealed by cryo-EM. Proc Natl Acad Sci,118(4):e2021180118.
    21. Zhang C, Wang YF, Zhu Y, Liu C, Gu C, Xu S, Wang YL, Zhou Y, Wang YX, Han W, Hong X, Yang Y, Zhang X, Wang T, Xu C, Hong Q, Wang S, Zhao Q, Qiao W, Zang J, Kong L, Wang F, Wang H, Qu D, Lavillette D, Tang H, Deng Q*, Xie Y*, Cong Y*, Huang Z*.(2021) Development and structural basis of a two-Mab cocktail for treating SARS-CoV-2 infections. Nat Commun,12:264.
    22. Xu C, Wang YX, Liu C, Zhang C, Han W, Hong X, Wang YF, Hong Q, Wang S, Zhao Q, Wang YL, Yang Y, Chen K, Zheng W, Kong L, Wang F, Zuo Q, Huang Z*, Cong Y*. (2021) Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Sci Adv, 7(1):eabe5575.
    23. Jin M, Liu C, Han W, Cong Y*. (2019) TRiC/CCT Chaperonin: Structure and Function. Macromolecular Protein Complexes II: Structure and Function, Subcellular Biochemistry, 93:625-654. (Book chapter, Springer Nature) 
    24. 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, 29:971–983.
    25. 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):19513–19522.
    26. 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, 73:1150-1161.
    27. 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.
    28. 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.
    29. Wang H, Han W, Takagi J*, Cong Y*. (2018) Yeast inner-subunit PA–NZ-1 labeling strategy for accurate subunit identification in a macromolecular complex through cryo-EM analysis. Journal of Molecular Biology,430(10):1417-1425.
    30. 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.
    31. 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
    32. 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.
    33. Jin M, Cong Y. (2017) Identification of an allosteric network that influences assembly and function of group II chaperonins. Nat Struct Mol Biol, 24:683–684.
    34. 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.
    35. 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, 27:373–385.
    36. 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 through high-resolution cryo-EM. Nat Struct Mol Biol, 23(12):1083-1091.
    37. 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.
    38. 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.
    39. 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.
    40. 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.
    41. 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.
    42. 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.
    43. 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.
    44. 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.
    45. 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.
    46. 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.
    47. 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.
    48. Leitner A, Joachimiak LA, Bracher A, M？nkemeyer 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.
    49. Cong Y, Schr？der 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.
    50. Zhang R, Hryc CF, Cong Y, Liu X, Jakana J, Gorchakov R, Baker ML, Weaver SC, Chiu W*. (2011) 4.4 ？ cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO Journal, 30(18):3854-3863.
    51. Cong Y, Ludtke SL. (2010) Single Particle Analysis at High Resolution. Methods in Enzymology, 482:211-235.
    52. 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 ？ Resolution Cryo-EM Structure of the Mammalian Chaperonin TRiC/CCT Reveals its Unique Subunit Arrangement. Proc Natl Acad Sci, 107(11):4967-4972.
    53. 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.
    54. 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.
    55. 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.
    56. 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.
    57. 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.
    58. 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.
    59. Kovacs JA, Chacón 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.
    60. 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.
    61. 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.
    62. 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 ABEEMσπ model on the basis of local HSAB principle and maximum hardness principle. Chem Phys Lett, 357:59-64.
    63. 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.
    64. 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.
    65. 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.
    66. 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.
    67. 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. 
    获奖及荣誉：
    研究组成员：

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