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韩爱东教授博导

邮  箱:ahan@xmu.edu.cn

职称/职务:教授 博士生导师

联系方式:
实验室主页

  • 个人简介
  • 科研领域
  • 代表性成果

1989年,南京大学植物学专业,学士学位;
1995年,中山大学遗传学专业,硕士学位;
1999年,中国科学院微生物研究所微生物学,博士学位;
1999-2007年,美国科罗拉多大学博德分校生化系,博士后/访问学者;
2006-2008年,美国南加州大学分子与计算生物系,访问学者;
2008年至今,澳门大阳城集团澳门大阳城集团2138网站,教授。
B.S. 1989, Nanjing University, Botany;
M.S. 1995, Sun Yat-Sen University, Genetics;
Ph.D. 1999, Institute of Microbiology, Chinese Academy of Sciences, Microbiology;
Postdoctoral Follow/Visiting Scholars, University of Colorado at Boulder, 1999-2007;
Senior Research Associate, University of Southern California, 2006-2008;
Professor, School of Life Sciences, Xiamen University, 2008 to Present.

课题组以结构生物学为主要的研究手段,揭示细胞的信号转导、物质运输、蛋白质翻译后修饰、以及微生物与宿主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。蛋白质的磷酸化修饰具有更广泛的表型和功能。我们也对tau蛋白的修饰、转运以及在神经退行性疾病中的作用机制等感兴趣,并开展相关药物的设计和研发。
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,并将信号传导至相连的调节蛋白(Response Regulator, RR),以调控各种生物学过程。这一调控系统被称为双组分系统(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,如金黄色葡萄球菌,肺炎链球菌等,引起脑膜炎、皮肤炎、鼻竇炎、肺炎等感染性疾病,更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WalK的晶体结构(图2),正试图解析带有细胞外感应结构域的全长WalRK复合体结构,以探索HAMP和PAS等结构域介导的信号转导和激酶活性调控机制,并积极研发新型抗生素。我们对革兰氏阴性细菌中的TCS也感兴趣。我们最近解析了一个钾离子感应系统KdpDE的复合体结构(图3)。
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. It is well known that protein phosphorylation by a variety of protein kinases play key roles in even broader biological processes. We are focusing our attention on tau phosphorylation, hoping to further our current understanding on its spreading and roles in neurodegenerative diseases.
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. With crystal or CroEM structures (Fig. 2), we hope to develop leading compounds for new antibiotics that may overcome the rapidly progressing antibiotic resistance in these pathogenic bacteria. We are also interested in some important TCSs in Gram-negative bacteria. As an example, we recently determined a complex structure of potassium sensing system KdpDE, revealing a unique model for specific recognition and signal transduction of a TCS (Fig. 3).

代表性论文(# co-first author, * Corresponding author):

1. Salamaga, B, Kong, L., Pasquina-Lemonche L., Lafage, L., Muhlen, M., Gibson, J., Grybchuk, D., Tooke, A., Panchal, V., Culp, E., Tatham, E.,O'Kane, M., Catley, T., Renshaw, S., Wright, G., Plevka, P., Bullough, P., Han, A*., Hobbs, J.* and Foster, S.*. Demonstration of the rol e of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics (2021). PNAS 118 (44): e2106022118
2. Liu, W., Li, X., Qi, H., Wu, Y., Qu, J., Yin, Z., Gao, X., Han, A*. and Shuai, J.* (2021). Biphasic regulation of transcriptional surge generated by the gene feedback loop in a two-component system, Bioinformatics 37 (17): 2682-2690
3. Xie, M, Wu, M, Han, A (2020). Structural insights into the signal transduction mechanism of the K+-sensing two-component system KdpDE. Science Signaling 13: eaaz2970.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Wang, C, Sang, J, Wang, J, Su, M, Downey, JS, Wu, Q, Wang, S, Cai, Y, Xu, X, Wu, J, Senadheera, DB, Cvitkovitch, DG, Chen, L, Goodman, SD 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.
10. Jayathilaka, N, Han, A, Gaffney, KJ, Dey, R, Jarusiewicz, JA, Noridomi, K, Philips, MA, Lei, X, He, J, Ye, J, Gao, T, Petasis, NA 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.
11. Mao, Y, Lin, J, Zhou, A, Ji, K, Downey, JS, Chen, R and Han, A(2011). "Quikgene: A gene synthesis method integrated with ligation-free cloning." Analytical Biochemistry 415 (1): 21-26.
12. He, J, Ye, J, Cai, Y, Riquelme, C, Liu, JO, 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.
13. Guo, L, Han, A, Bates, DL, 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.
14. Han, A, He, J, Wu, Y, Liu, JO 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.
15. Han, A, Pan, F, Stroud, JC, Youn, HD, Liu, JO and Chen, L (2003). "Sequence-specific recruitment of transcriptional co-repressor cabin1 by myocyte enhancer factor-2." Nature 422 (6933): 730-734.

荣誉、奖励及参加学术团体的情况: