科研领域描述
本实验室主要兴趣在于：
1. 生物的胁迫响应,包括衰老和休眠现象的分子机制 (Stress responses of living organisms: including the molecular mechanism of aging and dormancy) 2. 生物体内蛋白质-蛋白质相互作用的发生情况、机制、及生物学意义 (Mechanism and biological significance of protein-protein interactions)
任何生命形式都不可避免地要经历像高温、极端pH值、活性氧等有毒物质的存在等胁迫条件。在这样的条件下，生物体内的大分子，如DNA、RNA、蛋白质等由非共价弱相互作用维持的空间结构都将受到影响。这其中可能以蛋白质分子受到的威胁最大，蛋白质分子的去折叠往往会导致聚集的发生，而这将意味着蛋白质分子功能的丧失。过去的研究表明，各种生物的基因组都编码了一类被称为分子伴侣（或热休克蛋白、或胁迫蛋白等）的蛋白质分子。这些蛋白质的角色就是保护生物体内那些容易发生去折叠和聚集的蛋白质。这些“保镖”蛋白质，参与了对体内其它蛋白质分子的“生、老、病、死”等过程。我们关注的一些问题包括：胁迫蛋白质是如何在生物体内发挥其功能的？胁迫蛋白质分子的结构如何对胁迫条件发生瞬时响应而导致生物学活性顺时性提高的？部分生命个体以休眠方式应对极端胁迫条件的分子机制是什么？与此相关的衰老现象和休眠现象的分子机制是什么？等等。
蛋白质在生物体内发挥作用是通过与其它分子发生相互作用而完成的。大量的蛋白质分子自身或相互之间也发生着大量的相互作用。自身的相互作用，形成同源寡聚体，不同蛋白质分子之间的相互作用即形成异源寡聚体。尽管过去的体外或体内研究已经揭示了大量特异的蛋白质之间的相互作用，但大量发生于生物体内的动态的或弱的相互作用目前还难以鉴定和深入研究。我们关注的一些问题包括：很多通过体外研究被鉴定为以单亚基形式存在的蛋白质，在体内是否能够形成同源寡聚体？能够在活细胞条件下鉴定出与特异蛋白质发生相互作用的蛋白质？这样的以同源或异源寡聚形式发生的蛋白质-蛋白质相互作用如何完成特定的生物学功能？等等。
3. 革兰氏阴性细菌内外膜蛋白的生成转运、降解、质量控制、组装及生物活性调控等。主要通过活细胞体系开展研究，利用非天然氨基酸为探针对特定蛋白质进行遗传标记。
代表性论文
1. Anastasia N Ezemaduka, Jiayu Yu, Xiaodong Shi, Kaiming Zhang, Chang-Cheng Yin, Xinmiao Fu, and Zengyi Chang , A small heat shock protein enables Escherichia coli to grow at a lethal temperature of 50oC conceivably by maintaining cell envelope integrity , Journal of Bacteriology , 2014 , 196:11 2004-2011, doi:10.1128/JB.01473-14.
2. 昌增益 , 漫谈科学与科学研究（下） , 科学画报， , 2014 , 5月刊，44-45页。
3. Shanshan Li, Rui Wang, Deyong Li, Jing Ma, Heng Li, Xiaochuan He, Zengyi Chang* & Yuxiang Weng* , Thermal-triggerd Proteinquake Leads to Disassembly of DegP Hexamer as an Imperative Activation Step , Scientific Reports , 2014 , 4, 4834; DOI:10.1038/srep04834. , co-corresponding author
4. 昌增益 , 漫谈科学与科学研究（上） , 《科学画报》 , 2014 , 4月刊，46-47页。
5. Ge, X., Lyu, Z. X., Liu, Y., Wang, R., Zhao, X. S., Fu, X., and Chang, Z. , Identification of FkpA as a key quality control factor for the biogenesis of outer membrane proteins under heat shock conditions , Journal of Bacteriology , 2014 , 196(3):672-680.
6. Ge, X.,Wang, R., Ma, J., Liu, Y., Ezemaduka, A. N., Chen, P. R., Fu, X. and Chang, Z , DegP primarily functions as a protease for the biogenesis of β-barrel outer membrane proteins in the Gram-negative bacterium Escherichia coli , FEBS Journal , 2014 , 281(4):1226-1240; DOI: 10.1111/febs.12701 , [Full Text]
7. 昌增益 , 做一位称职的研究生导师 , 《研究生培养的国际视野》，人民出版社， , 2014 , 43-50页。
8. 昌增益 , 认识生命活动的直接执行者：神奇的蛋白质分子 , 《科学名家讲座》，中国言实出版社， , 2013 , 第十二辑，第59-85页
9. Fu, X., Shi, X., Yan, L., Zhang, H. and Chang, Z. , In vivo substrate diversity and preference of small heat shock protein IbpB as revealed by using a genetically incorporated photo-crosslinker. , J Biol Chem, , 2013 , 288:31646-31654.
10. Fu, X., Shi, X.D., Yin, L. X., Liu, J. F., Joo, K. H., Lee, J. Y., and Chang, Z., , Small heat shock protein IbpB acts as a robust chaperone in living cells by hierarchically activating its multi-type substrate-binding residues. , , J. Biol. Chem , 2013 , 288(17):11897-11906. , [Full Text]
11. 昌增益（郭久苓老师采访录） , 读未书之文，探不期之秘 , 《教学的魅力-北大生命科学名师访谈录》 （郭九苓 昌增益 柴真 主编）；北京大学出版社， , 2012 , 第109-120页。
12. Weizhe Hong, Ye E. Wu, Xinmiao Fu and Zengyi Chang , Chaperone-dependent mechanisms for acid resistance in enteric bacteria , Trends in Microbiology , 2012 , 20:328-335 , invited review
13. Dickinson, B. C., Tang, Y. Chang, Z. and Chang, C. J. , Development of a Nuclear-Localized Fluorescent Probe for Hydrogen Peroxide and Applications to the Study of Sirtuin-Mediated Oxidative Stress Responses in vivo , Chem. Biol , 2011 , 18:943-948 , corresponding author
14. Wu, S. Ge, X. Lv Z., Zhi Z., Chang, Z. and Zhao, X. S , Interaction between Bacterial Outer Membrane Proteins and Periplasmic Quality Control Factors: A Kinetic Partitioning Mechanism , Biochem. J. , 2011 , 438:505-511 , co-corresponding author
15. Xiaodong Shi, Zhao Wang, Linxuan Yan，Anastasia N. Ezemaduka, Guizhen Fan, Rui Wang, Xin-Miao Fu, Chang-Cheng Yin, Zengyi Chang , small heat shock protein AgsA forms dynamic fibrils , FEBS Letters , 2011 , 585:3396-3402
16. Zhang, M., Lin, S. Song, X. Liu, J. Fu, Y. Ge, X. Fu, X. Chang, Z. Chen, P. R. , A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance, , Nat. Chem. Biol. , 2011 , 7:671-677. , co-corresponding author and cover article
17. Zengyi Chang , Posttranslational modulation of Biological Activities of Molecular Chaperones , Science in China Series C: Life Sciences , 2009 , 52(6):515-520. , [Full Text] , Invited Critical Review
18. Zengyi Chang , The CUSBEA Program: Twenty Years Later , IUBMB Life , 2009 , 61:(6)555-565 (feature article)
19. FENG Yongjun, ZHANG Meng, HU Mingxi, ZHENG Jie, JIAO Wangwang & CHANG Zengyi , Disassembly Intermediates of RbsD Protein remain Oligomeric despite the loss of an intact secondary structure , Sci. China Ser. C-Life Sciences , 2009 , in press
20. Yunbiao Wang, Anastasia N. Ezemaduka, Yan Tang and Zengyi Chang , Understanding the Mechanism of the Dormant Dauer Formation of C. elegans: From Genetics to Biochemistry , IUBMB Life , 2009 , 61(6):607-612. , invited critical review
21. Jiang, J.S., Zhang, X. F., Chen, Y., Wu, Y., Zhou, Z. H., Chang, Z., Sui, S.F. , Activation of DegP Chaperone-Protease via Formation of Large Cage-like Oligomers upon Binding to Substrate Proteins , Proc. Natl. Acad. Sci. USA , 2008 , 105(33):11939-11944. , 通讯作者(corresponding author)
22. Jiao, W., Hong, W., Li, P., Sun, S., Ma, J., Qian, M., Hu, M., and Chang, Z. , The Dramatically Increased Chaperone Activity of Small Heat Shock Protein IbpB is Retained for an Extended Period of Time after the Stress Condition is Removed , Biochem. J. , 2008 , 15;410(1):63-70. , [Abstract]
23. Liu, C., Mao, K., Zhang, M., Sun, Z., Hong, W., Li, C., Peng, B., and Chang, Z. , The SH3-Like Domain Switches Its Interaction Partners to Modulate the Repression Activity of Mycobacterial Iron-Dependent Transcription Regulator (IdeR) in Response to Metal Ion Fluctuations , J. Biol. Chem. , 2008 , Vol. 283, Issue 4, 2439-2453 , [Abstract] , [Full Text]
24. Wu, Y., Hong, W., Zhang, L., and Chang, Z. , Conserved Amphiphilic Feature Is Essential for Periplasmic Chaperone HdeA to Support Acid Resistance in Enteric Bacteria , Biochem. J. , 2008 , 412:389-397. , [Abstract]
25. 马静， 葛熙、昌增益 , 蛋白质功能研究：历史、现状和将来 , 生命科学 , 2007 , 19（3）：294-300 , 应邀综述
26. Feng, Y., Jiao, W., Fu, X., and Chang, Z. , Stepwise Disassembly and Apparent Non-stepwise Reassembly for the Oligomeric RbsD Protein , Protein Science , 2006 , 15(6):1441-1448.
27. Fu, X., and Chang, Z , Identification of bis-ANS binding sites in Mycobacterium tuberculosis small heat shock protein Hsp16.3: Evidences for a two-step substrate-binding mechanism , Biochem. Biophys. Res. Commun. , 2006 , 349:169-171.
28. Hong, W., Jiao, W., Hu, J., Zhang, J., Liu, C., Fu, X., Shen, D., Xia, B., and Chang, Z. , Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation , J Biol Chem. , 2005 , Vol. 280, Issue 29, 27029-27034 , [Abstract] , [Full Text]
29. Jiao，W., Qian, M., Li, P., Zhao, L., and Chang, Z. , The essential role of the flexible termini in the temperature-responsiveness of the oligomeric state and chaperone-like activity for the polydisperse small heat shock protein IbpB from Escherichia coli , J Mol Biol. , 2005 , Volume 347, Issue 4, 8 April 2005, Pages 871-884 , [Full Text]
30. Fu, X., Zhang, H., Zhang, X., Cao, Y., Jiao, W., Liu, C., Song, Y., Abulimiti, A., and Chang, Z. , A dual role for the N-terminal region of Mycobacterium tuberculosis Hsp16.3 in self-oligomerization and binding denaturing substrate proteins , J Biol Chem. , 2005 , Vol. 280, Issue 8, 6337-6348 , [Abstract] , [Full Text]
31. Fu, X. and Chang ,Z. , Phylogenetic and biochemical studies reveal a potential evolutionary origin of animal small heat shock proteins from bacterial class A , J. Mol. Evol., , 2005 , 62:257-266.
32. Fu, X., Zhang, X., and Chang, Z. , 4'-dianilino-1,1'-binaphthyl-5,5'-sulfonate (bis-ANS), a novel molecule having chaperone-like activity , Biochem Biophys Res Commun., , 2005 , 329:1087-1093.
33. Jiao, W., Li, P., Zhang, J., Zhang, H., Chang, Z. , Small Heat Shock Proteins Function in the Insoluble Protein Complex , Biochem Biophys Res Commun., , 2005 , 335(1):227-231.
34. Zhang, H. Fu, X. Jiao, W., Zhang, X., Liu, C., and Chang, Z. , The association of small heat shock protein Hsp16.3 with the plasma membrane of Mycobacterium tuberculosis: dissociation of oligomers is a prerequisite , Biochem Biophys Res Commun., , 2005 , 330:1055-1061.
35. Zhang, X.,Fu, X., Zhang, H., Liu, C. Jiao, W., and Chang, Z. , Chaperone-like Activity of β-Casein , Interna. J. Biochem. Cell Biol., , 2005 , 37:1232-1240.
36. Liu Y., Fu, X., Shen, J., Zhang, H., Hong, W., and Chang, Z. , Periplasmic proteins of Escherichia coli are highly resistant to aggregation: reappraisal for roles of molecular chaperones in periplasm , Biochem Biophys Res Commun. , 2004 , Volume 316, Issue 3, 9 April 2004 , [Full Text]
37. Liu Y., Fu, X., Shen, J., Zhang, H., Hong, W., and Chang, Z. , Periplasmic proteins of Escherichia coli are highly resistant to aggregation: A reappraisal for roles of molecular chaperones in periplasm , Biochem Biophys Res Commun. , 2004 , 316(3):795-801.
38. Liu, C. He., Y. and Chang Z. , Truncated hemoglobin of Mycobacterium tuberculosis: The oligomeric state change and the interaction with membrane components , Biochem Biophys Res Commun. , 2004 , 316:1163-1172.
39. 昌增益 , 改变生物学进程的DNA双螺旋结构：纪念DNA双螺旋模型发现50周年 , 科学画报 , 2003 , 6月刊，24-25页。
40. Abulimiti, A., Fu, X., Gu., L., Feng, X., and Chang, Z. , Mycobacterium tuberculosis Hsp16.3 nonamers are assembled and re-assembled via trimer and hexamer intermediates , J Mol Biol. , 2003 , Volume 326, Issue 4, 28 February 2003, Pages 1013-1023 , [Full Text]
41. Abulimiti, A., Qiu, X., Chen, J., Liu, Y., and Chang, Z. , Reversible methionine sulfoxidation of Mycobacterium tuberculosis small heat shock protein Hsp16.3 and its possible role in scavenging oxidants , Biochem. Biophys. Res. Commun., , 2003 , 305(1):87-93.
42. Fu, X. Liu, C., Liu, Y., Feng, X., Gu, L., Chen, X., and Chang, Z. , Small Heat Shock Protein Hsp16.3 Modulates Its Chaperone Activity by Adjusting the Rate of Oligomeric Dissociation , Biochem Biophys Res Commun. , 2003 , 310(2):412-420.
43. Gu, L., Abulimiti, A., Li, W., and Chang, Z. , Monodisperse Hsp16.3 nonamer exhibits dynamic dissociation and reassociation, with the nonamer dissociation prerequisite for chaperone-like activity , J Mol Biol. , 2002 , Volume 319, Issue 2, 31 May 2002, Pages 517-526 , [Full Text]
44. Dai, H., Mao, Q., Yang, H., and Chang, Z. , Probing the Roles of the Only Universally Conserved Leucine Residue in the Oligomerization and Chaperone-like Activity of Mycobacterium tuberculosis Small Heat Shock Protein Hsp16.3 , J. Protein Chem.,（new name: Protein J.) , 2000 , 19(4):319-326.
45. Yang, H., Huang, S., Dai, H., Gong, Y., Zheng, C., and Chang, Z. , The Mycobacterium tuberculosis small heat shock protein Hsp16.3 exposes hydrophobic surfaces at mild conditions: conformational flexibility and molecular chaperone activity , Protein Sci. , 1999 , 8(1):174-179 , [Full Text]
46. Chang, Z., Primm, T.P., Jakana, J., Lee, I.H., Chiu, W., Gilb ert, H.F., and Quiocho, F.A. , Mycobacterium tuberculosis 16-kDa antigen (Hsp16.3) functions as an oligomeric structure in vitro to suppress thermal aggregation , J Biol Chem. , 1996 , 271(12):7218-23 , [Abstract] , [Full Text]
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