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韩爱东教授 博导
出处: 发布时间:2016-12-01 浏览次数:1772

韩爱东HAN Aidong, Ph.D.                             

韩爱东教授

授,博士生导师

电 话:+86-592-2188172

E-mail: ahan@xmu.edu.cn

homepage: http://ahan.xmu.edu.cn


19859月-19897, 南京大学/生物系, 学士学位

19929月-19957, 中山大学/遗传工程中心, 硕士学位

19955月-19998, 中国科学学院微生物研究所,博士学位

19999月-20065月,美国科罗拉多大学博德分校/生化系, 访问学者

20066月-20081月,美国南加州大学/分子与计算生物系, 访问学者

1999, Ph.D., Institute of Microbiology, Chinese Academy of Sciences; 

1999-2006, Postdoctoral follow, University of Colorado at Boulder; 

2006-2008, Senior research associate, University of Southern California.

 

研究领域(Research Area)

  

课题组主要以结构生物学技术为研究手段,揭示细胞的信号转导、物质运输、蛋白质翻译后修饰、与微生物相互作用等生理活动的分子机制。 在真核细胞中,蛋白质的乙酰化修饰通常发生在N末端和赖氨酸侧链上,是调节蛋白质功能,稳定性和细胞内定位的重要手段。N末端乙酰转移酶(NAT)负责蛋白质N末端乙酰化修饰(图1)。组蛋白乙酰转移酶(HAT)和组蛋白去乙酰化酶(HDAC)负责赖氨酸侧链的乙酰化修饰,是表观遗传学调控基因转录的一个关键手段。在细胞的编程和重编程过程中,HAT和HDAC 作为转录辅因子与各种转录因子相互作用(图2),在转录调控中起到至关重要的作用。

在原核细胞中,组氨酸激酶(Sensor histidine Kinase, SK)负责刺激依赖的组氨酸磷酸化,并将信号传导至相关的调节蛋白(Response Regulator, RR),以调控各种各样的生物学过程。这一调控系统被称作双组分系统(Two-Component System, TCS)。基因表达的转录调控是TCS的一个主要功能 。一些常见的革兰氏阳性细菌引起脑膜炎、皮肤炎、鼻竇炎、肺炎等感染性疾病,又容易产生抗生素的耐药性。WalRK, 也叫VicRK或YycFG是这些细菌中关键的TCS。课题组解析了完整的胞内VicK的晶体结构(图3),以探索其HAMP和PAS结构域的信号转导和激酶活性,研究VicK调控VicR转录活性的分子机制,并在此为基础,积极开展新型抗生素的研发工作。

My lab is interested in understanding molecular mechanisms of several key biological processes, including signal transduction through membrane, intracellular trafficking, protein post-translational modification (PTM), and microbe-host interaction. Protein acetylation, one of important PTMs, regulates protein function, stability and cellular localizations in eukaryotic cells. Proteins can be acetylated at the amine group of peptidic N-terminus and lysine side chain. A group of proteins called N-terminal acetyltransferases (NAT) acetylate protein N-terminus (Fig. 1). The lysine acetylation as one of important means for epigenetic regulations in transcription is carried out reversibly by histone acetyltransferases (HAT) and histone deacetylases (HDAC), which often form high-order regulatory complexes (Fig. 2) with a variety of transcription factors, such as myocyte enhancer factor 2 (MEF2) to globally program and reprogram the cells. In prokaryotic cells, two-component system (TCS), including histidine kinase (SK) and response regulator (RR), is responsible for a diverse of biological processes, one of which is stimuli induced transcription. Our lab uses WalRK, also called VicRK or YycFG, an essential TCS in several Gram-positive bacteria as a model system to understand how intra/extracellular signals regulate the gene transcription for bacterial survival under stress environments and develop leading compounds for new antibiotics with a hope to overcome the rapidly progressing antibiotic resistance in these pathogenic bacteria.  


代表性论文(Selected Publications)

1.Wang, X, Kondakova, AN, Zhu, Y, Knirel, YA, Han, A. (2017). The O-antigen structure of bacterium Comamonas aquatica CJG. Microbiology 163(11):1637-1640.

2.Cai, Y, Su M, Ahmad, A, Hu, X, Sang, J, Kong, L, Chen, X, Wang, C, Shuai, J, Han, A. (2017). Conformational dynamics of the essential sensor histidine kinase WalK. Acta Crystallography D Structure Biololgy 73 (Pt 10):793-803.

3.Hong, H., Cai, Y., Zhang, S., Ding, H., Wang, H. and Han, A. (2017). “Molecular basis of substrate specific acetylation by N-terminal acetyltransferase NatB.” Structure 25 (4): 641-9.

4.Shi, S., Liu, K., Chen, Y., Zhang, S., Lin, J., Gong, C., Jin, Q., Yang, X., Chen, R., Ji, Z. and Han, A. (2016). “Competitive inhibition of lysine acetyltransferase 2B by a small motif of the adenoviral oncoprotein E1A.” Journal of Biological Chemistry 291 (27): 14363-72.

5.Ahmad, A., Cai, Y., Chen, X., Shuai, J. and Han, A. (2015). Conformational dynamics of response regulator regx3 from Mycobacterium tuberculosis. PLoS One 10 (7): e0133389.

6.Shi, S., Lin, J., Cai, Y., Yu, J., Hong, H., Ji, K., Downey, J. S., Lu, X., Chen, R., Han, J. and Han, A. (2014). Dimeric structure of p300/cbp associated factor. BMC Structural Biology 14: 2.

7.Wang, C., Sang, J., Wang, J., Su, M., Downey, J. S., Wu, Q., Wang, S., Cai, Y., Xu, X., Wu, J., Senadheera, D. B., Cvitkovitch, D. G., Chen, L., Goodman, S. D. and Han, A. (2013). Mechanistic insights revealed by the crystal structure of a histidine kinase with signal transducer and sensor domains. PLoS Biology 11 (2): e1001493.

8.Jayathilaka, N., Han, A., Gaffney, K. J., Dey, R., Jarusiewicz, J. A., Noridomi, K., Philips, M. A., Lei, X., He, J., Ye, J., Gao, T., Petasis, N. A. and Chen, L. (2012). Inhibition of the function of class iia hdacs by blocking their interaction with mef2. Nucleic Acids Research 40(12): 5378-5388.

9.Mao, Y., Lin, J., Zhou, A., Ji, K., Downey, J. S., Chen, R. and Han, A. (2011). Quikgene: A gene synthesis method integrated with ligation-free cloning. Analytical Biochemistry 415 (1): 21-26.

  

10.He, J., Ye, J., Cai, Y., Riquelme, C., Liu, J. O., Liu, X., Han, A. and Chen, L. (2011). Structure of p300 bound to mef2 on DNA reveals a mechanism of enhanceosome assembly. Nucleic Acids Research 39 (10): 4464-4474.

11.Wu, Y., Dey, R., Han, A., Jayathilaka, N., Philips, M., Ye, J. and Chen, L. (2010). Structure of the mads-box/mef2 domain of mef2a bound to DNA and its implication for myocardin recruitment. Journal of Molecular Biology 397 (2): 520-533.

12.Guo, L., Han, A., Bates, D. L., Cao, J. and Chen, L. (2007). Crystal structure of a conserved n-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains. Proceedings of the National Academy of Science USA 104 (11): 4297-4302.

13.Han, A., He, J., Wu, Y., Liu, J. O. and Chen, L. (2005). Mechanism of recruitment of class ii histone deacetylases by myocyte enhancer factor-2. Journal of Molecular Biology 345 (1): 91-102.

14.Han, A., Pan, F., Stroud, J. C., Youn, H. D., Liu, J. O. and Chen, L. (2003). Sequence-specific recruitment of transcriptional co-repressor cabin1 by myocyte enhancer factor-2. Nature 422 (6933): 730-734.


 

参加学术团体的情况Professional service

  

中国生物化学和分子生物学会会员

中国生物物理学会会员

美国心脏和中风学会会员

国际期刊NAR,JMB,JBC等的审稿人