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首頁 全所PI名錄
  • 叢堯
  • 研究員，研究組長，博士生導師
  • E-mail: cong@@sibcb.ac.cn
  • 實驗室主頁: 
    個人簡介：

  • 　　1995年7月遼寧師范大學獲學士學位;2000年7月吉林大學獲博士學位。2000年9月至2001年10月，在中科院大連化學物理研究所從事博士后研究工作。2001年11月至2005年5月，先后在美國Scripps研究所及德州大學休斯頓健康信息中心的Willy Wriggers研究組任博士后。其中2004年1月至2005年12月獲美國W. M. Keck 基金會Postdoctoral Fellowship資助。2005年6月至2011年7月，美國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與細胞所研究員、博士生導師。獲國家基金委“優秀青年”(2013年)基金資助。

    社會任職：
    研究方向：
  • 蛋白質質量控制大分子機器的結構與功能
    研究工作：

  • 　　本研究組致力于解析分子伴侶協助下的蛋白質折疊與解聚的機理。主要實驗手段包括超低溫冷凍電鏡(cryo-EM)單顆粒重組以及低溫電子斷層掃描技術(cryo-Electron Tomography)，并結合生物信息學和分子柔性裝配等計算工具。

    　　蛋白質折疊中的缺陷通常伴隨著許多人類疾病，包括癌癥及蛋白聚集引起的神經退行性疾病，如帕金森氏綜合癥和亨廷頓舞蹈病等。分子伴侶(chaperone)是一類可以協助細胞中蛋白質正確折疊的分子機器，其中真核細胞中雙環背對背堆疊的多聚體分子伴侶素(chaperonin)TRiC/CCT是最為復雜的分子伴侶。它可以幫助~5-10%胞質蛋白的折疊，包括許多重要的結構和調節蛋白。然而，由于其結構的復雜性導致對此重要分子機器的結構知之甚少。我們的研究興趣在于解析分子伴侶如TRiC是如何識別并結合它的底物，三磷酸腺苷(ATP)觸發下其構象變化與底物蛋白正確折疊之間的相互關系。長期著眼，我們會進一步研究重要分子伴侶極其cochaperone之間如何相互作用來共同協助底物蛋白質的折疊與解聚。

    　　我們的另外一個研究方向是二維圖像對位(image alignment)方法及分子柔性裝配(flexible fitting)工具的發展及其在cryo-EM數據處理中的應用。我們發展了創新性的二維快速轉動匹配方法，簡稱FRM2D。該方法不僅計算精度高于傳統方法并且極大縮減了計算時間。此方法已成功應用于十余個中、高分辨率大分子復合物結構的三維重組過程中。此外，FRM2D方法已被嵌入冷凍電鏡領域三大應用最廣泛的單顆粒重組軟件包之一EMAN之中，供其在世界范圍內的用戶免費使用。

    承擔科研項目情況：
    代表論著：
    1. Tan Y, Li J, Zhang S, Zhang Y, Zhuo Z, Ma X, Yin Y, Jiang Y, Cong Y*, Meng G*. (2024)Cryo-EM structure of PML RBCC dimer reveals CC-mediated octopus-like nuclear body assembly mechanism. Cell Discov, 10,118.
    2. Hong Q, Wang S, Wang X, Han W, Chen T, Liu Y, Cheng F, Qin S, Zhao S, Liu Q, Cong Y*, Huang Z*. (2024)Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles. Vaccines, 12(9): 1077.
    3. Zhao Q, Hong X, Wang Y, Zhang S, Ding Z, Meng X, Song Q, Hong Q, Jiang W, Shi X, Cai T, Cong Y*.(2024) An immobilized antibody-based affinity grid strategy for on-grid purification of target proteins enables high-resolution cryo-EM. Commun Biol, 7:715.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. 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.
    15. 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.
    16. 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.
    17. 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.
    18. 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.
    19. 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.
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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.
    25. 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.
    26. 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)?
    27. 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.
    28. 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.
    29. 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.
    30. 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.
    31. 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.
    32. 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.
    33. 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.
    34. 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
    35. 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.
    36. 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.
    37. 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.
    38. 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.
    39. 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.
    40. 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.
    41. 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.
    42. 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.
    43. 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.
    44. 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.
    45. 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.
    46. 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.
    47. 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.
    48. 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.
    49. 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.
    50. 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.
    51. 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.
    52. 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.
    53. 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.
    54. Cong Y, Ludtke SL. (2010) Single Particle Analysis at High Resolution. Methods in Enzymology, 482:211-235.
    55. 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.
    56. 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.
    57. 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.
    58. 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.
    59. 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.
    60. 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.
    61. 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.
    62. 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.
    63. 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.
    64. 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.
    65. 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.
    66. 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.
    67. 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.
    68. 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.
    69. 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.
    70. 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.?
    獲獎及榮譽：
    研究組成員：

  • 合影

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