基本信息
丛尧  女  博导  中国科学院分子细胞科学卓越创新中心(生物化学与细胞生物学研究所)
电子邮件: cong@sibcb.ac.cn
通信地址: 上海市浦东新区海科路333号B421
邮政编码: 201210
部门/实验室:生物化学与细胞生物学研究所

研究领域


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及其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。

招生信息

   
招生专业
071010-生物化学与分子生物学
085238-生物工程
招生方向
结构生物学
结构生物学

教育背景

1995-09--2000-07   吉林大学   博士
1991-09--1995-07   辽宁师范大学   学士
学历
博士

学位
博士

工作经历

   
工作简历
2011-07~现在, 中国科学院上海生命科学研究院生物化学与细胞生物学研究所, 研究员
2010-10~2011-06,美国贝勒医学院国家大分子影像中心, 讲师
2005-06~2010-09,美国贝勒医学院国家大分子影像中心, 助理研究员
2003-05~2005-05,美国德州大学休斯顿健康科学中心, 博士后
2001-11~2003-04,美国Scripps研究所, 博士后
社会兼职
2016-04-24-今,上海生物物理学会, 理事
2016-01-01-2020-12-31,中国电子显微镜协会, 理事
2014-10-01-今,Biophysics Reports, 编委
2013-07-10-今,上海生物物理学会电镜专业委员会, 主任
2013-07-10-今,中国生物物理学会分子生物物理专业委员会, 理事

出版信息

   
发表论文

1. Chen J, Zhang C, Zhou Y, Zhang X, Shen C, Ye X, Jiang W, Huang Z* and Cong Y* (2017) A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. Journal of Virology, doi:10.1128/JVI.01257-17

2. 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* (2017) Structure, Immunogenicity and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid. Journal of Virology, 92, e01330-17.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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, doi:10.1038/srep34174.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. Cong Y, Ludtke SL. (2010) Single Particle Analysis at High Resolution. Methods in Enzymology, 482:211-235.

22. 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.

23. 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.                                                     

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

 


专利与奖励

   
奖励信息
(1) 上海市生物物理学科优秀女青年科技工作者, 市地级, 2015
(2) 国家基金委优秀青年, 国家级, 2012
(3) 中科院“百人计划”, 研究所(学校), 2012
专利成果
   

科研活动

科研项目
( 1 ) 基于超低温冷冻电镜的蛋白酶体结构与功能研究, 主持, 国家级, 2013-01--2016-12
( 2 ) 近原子分辨成像和三维重构技术, 主持, 部委级, 2014-01--2018-12
( 3 ) 应用国家蛋白质科学研究(上海)设 施分子影像技术探索染色质的组装与重塑, 主持, 省级, 2013-07--2016-08
( 4 ) 蛋白质复合物调控染色体结构的分子机理, 主持, 国家级, 2013-01--2017-08
( 5 ) 基于冷冻电镜的真核细胞分子伴侣素TRiC的结构与功能研究, 主持, 国家级, 2017-01--2020-12
( 6 ) 开发基于病毒样颗粒的新型疫苗关键技术平台, 主持, 部委级, 2015-01--2016-12
( 7 ) 脂代谢相关蛋白的免疫调控功能研究, 参与, 部委级, 2017-01--2021-12
( 8 ) 细胞运动关键辅助蛋白复合物的结构、组装与功能, 参与, 国家级, 2017-07--2022-06
( 9 ) 电镜系统的Titan Krios冷冻电镜升级改造, 主持, 部委级, 2018-01--2020-12
参与会议
(1)ATP Triggered Opposite Modes of Action of the ATPases in Protein Quality Control Revealed by Cryo-EM   2017-06-09
(2)ATP Triggered Opposite Modes of Action of the ATPases in Protein Quality Control Revealed by Cryo-EM   2017-05-17
(3)Stepwise nucleotide-binding mechanism of eukaryotic chaperonin TRiC/CCT revealed by high-resolution cryo-EM   2016-06-24
(4)Cryo-EM visualization of antibody-virus complex   2016-01-12
(5)Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM   2015-06-03
(6)Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM   2015-05-09
(7)Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM   2015-05-07
(8)Structural basis for recognition of human enterovirus 71 by a broadly neutralizing monoclonal antibody revealed by cryo-EM   2015-04-23
(9)Cryo-EM of asymmetric and dynamic protein folding nanomachineTRiC   2014-07-26
(10)Proteins in disease I   2014-05-17
(11)Cryo-EM Study on Asymmetric and Dynamic Protein Folding NanomachineTRiC   2014-05-12
(12)Cryo-EM Study on Asymmetric and Dynamic Macromolecular Machine TRiC   2013-12-07
(13)Cryo-EM Study on Asymmetric and Dynamic Macromolecular Machine TRiC   2013-10-15
(14)2D Image Alignment and Classification   2013-07-10
(15)Symmetry-Free Cryo-EM Structures of the Chaperonin TRiC Along its ATPase-Driven Conformational Cycle   2012-09-07
(16)Symmetry-Free Cryo-EM Structures of the Chaperonin TRiC Along its ATPase-Driven Conformational Cycle   2012-01-05
(17)Structural Characterization of the Eukaryotic Chaperonin TRiC/CCT by cryo-EM, NCMI Workshop on Single Particle Reconstruction   2011-03-14

合作情况

   
项目协作单位
   

指导学生

已指导学生

丁占玉  博士研究生  071010-生物化学与分子生物学  

臧云祥  博士研究生  071010-生物化学与分子生物学  

刘向阳  硕士研究生  085238-生物工程  

付政麟  硕士研究生  085238-生物工程  

王胡萍  硕士研究生  085238-生物工程  

现指导学生

陈进寰  博士研究生  071010-生物化学与分子生物学  

徐聪  博士研究生  071010-生物化学与分子生物学  

郑伟  博士研究生  071010-生物化学与分子生物学  

金明梁  博士研究生  071010-生物化学与分子生物学  

张翔  硕士研究生  085238-生物工程  

韩文玉   硕士研究生  071008-发育生物学  

刘彩璇  博士研究生  071010-生物化学与分子生物学  

汪一帆  博士研究生  071010-生物化学与分子生物学  

洪晓喻  硕士研究生  085238-生物工程