叢堯

叢堯

叢堯，女，中國科學院大學專任教師。

基本介紹

  • 中文名：叢堯
  • 國籍：中國
  • 畢業院校：遼寧師範大學
  • 學位/學歷：博士
人物經歷,教育背景,工作經歷,社會兼職,研究方向,科研成果,發表論文,科研項目,

人物經歷

教育背景

1995-09--2000-07 吉林大學 博士
1991-09--1995-07 遼寧師範大學 學士

工作經歷

2011-07~現在, 中國科學院上海生命科學研究院生物化學與細胞生物學研究所, 研究員
2010-10~2011-06,美國貝勒醫學院國家大分子影像中心, 講師
2005-06~2010-09,美國貝勒醫學院國家大分子影像中心, 助理研究員
2003-05~2005-05,美國德州大學休斯頓健康科學中心, 博士後
2001-11~2003-04,美國Scripps研究所, 博士後

社會兼職

2019-07-01-今,Scientific Reports, 編委
2016-04-24-今,上海生物物理學會, 理事
2016-01-01-2020-12-31,中國電子顯微鏡協會, 理事
2014-10-01-今,Biophysics Reports, 編委
2013-07-10-今,上海生物物理學會電鏡專業委員會, 主任
2013-07-10-今,中國生物物理學會分子生物物理專業委員會, 理事

研究方向

本研究組致力於解析分子伴侶協助下的蛋白質摺疊與解聚的機理。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)，並結合生物信息學和分子柔性裝配等計算工具。
蛋白質摺疊中的缺陷通常伴隨著許多人類疾病，包括癌症及蛋白聚集引起的神經退行性疾病，如帕金森氏綜合症和亨廷頓舞蹈病等。分子伴侶(chaperone)是一類可以協助細胞中蛋白質正確摺疊的分子機器，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是最為複雜的分子伴侶。它可以幫助~5-10%胞質蛋白的摺疊，包括許多重要的結構和調節蛋白。然而，由於其結構的複雜性導致對此重要分子機器的結構知之甚少。我們的研究興趣在於解析分子伴侶如TRiC是如何識別並結合它的底物，三磷酸腺苷(ATP)觸發下其構象變化與底物蛋白正確摺疊之間的相互關係。長期著眼，我們會進一步研究重要分子伴侶及其cochaperone之間如何相互作用來共同協助底物蛋白質的摺疊與解聚。
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數據處理中的套用。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於傳統方法並且極大縮減了計算時間。此方法已成功套用於十餘箇中、高解析度大分子複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套用最廣泛的單顆粒重組軟體包之一EMAN之中，供其在世界範圍內的用戶免費使用。

科研成果

發表論文

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Jin M, Liu C, Han W, Cong Y*. (2020) TRiC/CCT Chaperonin: Structure and Function. Macromolecular Protein Complexes II: Structure and Function, Subcellular Biochemistry, 93:625-654. (Book chapter, Springer Nature)
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. Cong Y, Ludtke SL. (2010) Single Particle Analysis at High Resolution. Methods in Enzymology, 482:211-235.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.

科研項目

（ 1 ） 基於超低溫冷凍電鏡的蛋白酶體結構與功能研究, 主持, 國家級, 2013-01--2016-12
（ 2 ） 近原子分辨成像和三維重構技術, 主持, 部委級, 2014-01--2018-12
（ 3 ） 套用國家蛋白質科學研究(上海)設 施分子影像技術探索染色質的組裝與重塑, 主持, 省級, 2013-07--2016-08
（ 4 ） 蛋白質複合物調控染色體結構的分子機理, 主持, 國家級, 2013-01--2017-08
（ 5 ） 基於冷凍電鏡的真核細胞分子伴侶素TRiC的結構與功能研究, 主持, 國家級, 2017-01--2020-12
（ 6 ） 開發基於病毒樣顆粒的新型疫苗關鍵技術平台, 主持, 部委級, 2015-01--2016-12
（ 7 ） 脂代謝相關蛋白的免疫調控功能研究, 參與, 部委級, 2017-01--2021-12
（ 8 ） 細胞運動關鍵輔助蛋白複合物的結構、組裝與功能, 參與, 國家級, 2017-07--2022-06
（ 9 ） 電鏡系統的Titan Krios冷凍電鏡升級改造, 主持, 部委級, 2018-01--2020-12
（ 10 ） 行動中的蛋白酶體：從底物識別、處理到水解的機制研究, 主持, 國家級, 2019-01--2021-12
（ 11 ） 基於冷凍電鏡的組蛋白H3K4甲基轉移酶COMPASS複合體的結構與功能研究, 主持, 國家級, 2019-01--2022-12
（ 12 ） 冷凍電鏡原位結構動態分析技術, 主持, 部委級, 2020-01--2024-12
（ 13 ） 基於冷凍電鏡的蛋白酶體底物降解機制及特異性抗體中和新冠病毒的結構機制研究, 主持, 研究所（學校）, 2020-10--2023-09
參與會議
（1）新冠病毒結合受體及特異性抗體中和新冠病毒的結構機制研究 第十八次中國生物物理學會 2020-11-16
（2）Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM 第八屆細胞結構與功能的信號基礎研討會 2020-10-29
（3）新冠病毒結合受體及特異性抗體中和新冠病毒的結構機制研究 2020年全國電子顯微學術年會 2020-10-21
（4） Proteasome in Action Revealed by Near-atomic Resolution Cryo-EM 2019-12-16
（5）An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity 2019-10-16
（6）An ensemble of cryo-EM structures of TRiC reveals its conformational landscape and subunit specificity 2019-09-14
（7）Atomic-resolution Cryo-EM Structure Based Vaccine and Drug Discovery against Enterovirus 2019-03-21
（8）Protein Quality Control Nanomachine in Action Revealed by Near-atomic Resolution Cryo-EM 2018-10-23
（9）ATP Triggered Opposite Modes of Action of the ATPase in Protein 2018-05-03
（10）“Ensemble of cryo-EM structures of eukaryotic chaperonin TRiC/CCT reveals its stepwise ring closure mechanism” 2018-04-17
（11）ATP Triggered Opposite Modes of Action of the ATPases in Protein Quality Control Revealed by Cryo-EM 2018-04-06
（12）ATP Triggered Opposite Modes of Action of the ATPases in Protein Quality Control Revealed by Cryo-EM 2017-06-09
（13）ATP Triggered Opposite Modes of Action of the ATPases in Protein Quality Control Revealed by Cryo-EM 2017-05-17
（14）(18) Stepwise nucleotide-binding mechanism of eukaryotic chaperonin TRiC/CCT revealed by high-resolution cryo-EM 2017-05-17
（15）Stepwise nucleotide-binding mechanism of eukaryotic chaperonin TRiC/CCT revealed by high-resolution cryo-EM 2016-06-24
（16）Cryo-EM visualization of antibody-virus complex 2016-01-12
（17）Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM 2015-06-03
（18）Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM 2015-05-09
（19）Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM 2015-05-07
（20）Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM 2015-04-23
（21）Cryo-EM of asymmetric and dynamic protein folding nanomachineTRiC 2014-07-26
（22）Proteins in disease I 2014-05-17
（23）Cryo-EM Study on Asymmetric and Dynamic Protein Folding NanomachineTRiC 2014-05-12
（24）Cryo-EM Study on Asymmetric and Dynamic Macromolecular Machine TRiC 2013-12-07
（25）Cryo-EM Study on Asymmetric and Dynamic Macromolecular Machine TRiC 2013-10-15
（26）2D Image Alignment and Classification 2013-07-10
（27）Symmetry-Free Cryo-EM Structures of the Chaperonin TRiC Along its ATPase-Driven Conformational Cycle 2012-09-07
（28）Symmetry-Free Cryo-EM Structures of the Chaperonin TRiC Along its ATPase-Driven Conformational Cycle 2012-01-05
（29）Structural Characterization of the Eukaryotic Chaperonin TRiC/CCT by cryo-EM, NCMI Workshop on Single Particle Reconstruction 2011-03-14

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