Contact information

Email:hanzhifu@mail.tsinghua.edu.cn

Zhifu Han Ph.D.

Funding:
1. Structural and functional studies of plant Malectin-like receptor kinases (the National Natural Science Foundation of China, No. 31971119, 2020.01-2023.12)
2. Ligand recognition and activation mechanism of plant LRR receptor-like proteins in plant immunity (the National Natural Science Foundation of China, No. 32171193, 2022.01- 2025.12)

Awards:
(1) Han Zhifu (3/5) ; The structure and function of BRI1 receptor kinases, the 2nd Prize of National Natural Science of China in 2017(ranked 3rd) (Chai Jijie; Chang Junbiao; Han Zhifu; Li Lei; Song Chuanjun).
(2) Han Zhifu (4/10) ; Interaction between small molecules and proteins, the first prize of scientific and technological progress of Henan Province, 2016 (Chang Junbiao; Chai Jijie; Wang Ruiyong; Han Zhifu; Song Chuanjun; Yu Wenquan; Wu Jie; Wang Jizong; Lin Guangzhong).

Resume

1991-1996Shanxi Medical University B.S.

1997-2000Shanxi Medical University M.S.

2000-2003Peking Union Medical College Ph.D.

2004-2010National Institute of Biological Sciences, Beijing Research Assistant

2011-2017School of Life sciences, Tsinghua University Research Assistant

2017-PresentSchool of Life sciences, Tsinghua University Research Associate Professor

Main Reaearch Fields

Structural study of plant receptor-like kinases and NLR proteins.

Selected Publications


1.            C. Liu, L. Shen, Y. Xiao, D. Vyshedsky, C. Peng, X. Sun, Z. Liu, L. Cheng, H. Zhang, Z. Han, J. Chai, H. M. Wu, A. Y. Cheung, C. Li, Pollen PCP-B peptides unlock a stigma peptide-receptor kinase gating mechanism for pollination. Science 372, 171-175 (2021).

2.            M. Huang, X. Zhang, G. A. Toh, Q. Gong, J. Wang, Z. Han, B. Wu, F. Zhong, J. Chai, Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Nature 592, 773-777 (2021).

3.            S. Hou, D. Liu, S. Huang, D. Luo, Z. Liu, Q. Xiang, P. Wang, R. Mu, Z. Han, S. Chen, J. Chai, L. Shan, P. He, The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phytocytokines and microbes. Nature communications 12, 5494 (2021).

4.            Y. Xiong, Z. Han, J. Chai, Resistosome and inflammasome: platforms mediating innate immunity. Current opinion in plant biology 56, 47-55 (2020).

5.            Y. Wang, L. A. Graham, Z. Han, R. Eves, A. K. Gruneberg, R. L. Campbell, H. Zhang, P. L. Davies, Carrot 'antifreeze' protein has an irregular ice-binding site that confers weak freezing point depression but strong inhibition of ice recrystallization. The Biochemical journal 477, 2179-2192 (2020).

6.            L. Sun, Y. Peng, W. Yu, Y. Zhang, L. Liang, C. Song, J. Hou, Y. Qiao, Q. Wang, J. Chen, M. Wu, D. Zhang, E. Li, Z. Han, Q. Zhao, X. Jin, B. Zhang, Z. Huang, J. Chai, J. H. Wang, J. Chang, Mechanistic Insight into Antiretroviral Potency of 2'-Deoxy-2'-beta-fluoro-4'-azidocytidine (FNC) with a Long-Lasting Effect on HIV-1 Prevention. Journal of medicinal chemistry 63, 8554-8566 (2020).

7.            S. Ma, D. Lapin, L. Liu, Y. Sun, W. Song, X. Zhang, E. Logemann, D. Yu, J. Wang, J. Jirschitzka, Z. Han, P. Schulze-Lefert, J. E. Parker, J. Chai, Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme. Science 370,  (2020); published online EpubDec 4 (10.1126/science.abe3069).

8.            X. Yang, G. Lin, Z. Han, J. Chai, Structural Biology of NOD-Like Receptors. Advances in experimental medicine and biology 1172, 119-141 (2019)10.1007/978-981-13-9367-9_6).

9.            Y. Xiao, M. Stegmann, Z. Han, T. A. DeFalco, K. Parys, L. Xu, Y. Belkhadir, C. Zipfel, J. Chai, Mechanisms of RALF peptide perception by a heterotypic receptor complex. Nature 572, 270-274 (2019).

10.          J. Wang, J. Wang, M. Hu, S. Wu, J. Qi, G. Wang, Z. Han, Y. Qi, N. Gao, H. W. Wang, J. M. Zhou, J. Chai, Ligand-triggered allosteric ADP release primes a plant NLR complex. Science 364,  (2019); published online EpubApr 5 (10.1126/science.aav5868).

11.          J. Wang, M. Hu, J. Wang, J. Qi, Z. Han, G. Wang, Y. Qi, H. W. Wang, J. M. Zhou, J. Chai, Reconstitution and structure of a plant NLR resistosome conferring immunity. Science 364,  (2019); published online EpubApr 5 (10.1126/science.aav5870).

12.          J. Tang, Y. Sun, Z. Han, W. Shi, An illustration of optimal selected glycosidase for N-glycoproteins deglycosylation and crystallization. International journal of biological macromolecules 122, 265-271 (2019).

13.          G. Huang, J. Sun, J. Bai, Y. Han, F. Fan, S. Wang, Y. Zhang, Y. Zou, Z. Han, D. Lu, Identification of critical cysteine sites in brassinosteroid-insensitive 1 and novel signaling regulators using a transient expression system. The New phytologist 222, 1405-1419 (2019).

14.          L. Dong, X. Guan, N. Li, F. Zhang, Y. Zhu, K. Ren, L. Yu, F. Zhou, Z. Han, N. Gao, Z. Huang, An anti-CRISPR protein disables type V Cas12a by acetylation. Nature structural & molecular biology 26, 308-314 (2019).

15.          X. Yang, F. Yang, W. Wang, G. Lin, Z. Hu, Z. Han, Y. Qi, L. Zhang, J. Wang, S. F. Sui, J. Chai, Structural basis for specific flagellin recognition by the NLR protein NAIP5. Cell research 28, 35-47 (2018).

16.          R. Wang, Z. Han, B. Liu, B. Zhou, N. Wang, Q. Jiang, Y. Qiao, C. Song, J. Chai, J. Chang, Identification of Natural Compound Radicicol as a Potent FTO Inhibitor. Molecular pharmaceutics 15, 4092-4098 (2018).

17.          X. Zhang, W. Liu, T. T. Nagae, H. Takeuchi, H. Zhang, Z. Han, T. Higashiyama, J. Chai, Structural basis for receptor recognition of pollen tube attraction peptides. Nature communications 8, 1331 (2017).

18.          Z. Wu, S. Liang, W. Song, G. Lin, W. Wang, H. Zhang, Z. Han, J. Chai, Functional and Structural Characterization of a Receptor-Like Kinase Involved in Germination and Cell Expansion in Arabidopsis. Frontiers in plant science 8, 1999 (2017)10.3389/fpls.2017.01999).

19.          W. Song, Z. Han, J. Wang, G. Lin, J. Chai, Structural insights into ligand recognition and activation of plant receptor kinases. Current opinion in structural biology 43, 18-27 (2017).

20.          S. Mou, X. Zhang, Z. Han, J. Wang, X. Gong, J. Chai, CLE42 binding induces PXL2 interaction with SERK2. Protein & cell 8, 612-617 (2017).

21.          C. Ma, Y. Liu, B. Bai, Z. Han, J. Tang, H. Zhang, H. Yaghmaiean, Y. Zhang, J. Chai, Structural basis for BIR1-mediated negative regulation of plant immunity. Cell research 27, 1521-1524 (2017).

22.          G. Lin, L. Zhang, Z. Han, X. Yang, W. Liu, E. Li, J. Chang, Y. Qi, E. D. Shpak, J. Chai, A receptor-like protein acts as a specificity switch for the regulation of stomatal development. Genes & development 31, 927-938 (2017).

23.          H. Zhang, X. Lin, Z. Han, J. Wang, L. J. Qu, J. Chai, SERK Family Receptor-like Kinases Function as Co-receptors with PXY for Plant Vascular Development. Molecular plant 9, 1406-1414 (2016).

24.          H. Zhang, X. Lin, Z. Han, L. J. Qu, J. Chai, Crystal structure of PXY-TDIF complex reveals a conserved recognition mechanism among CLE peptide-receptor pairs. Cell research 26, 543-555 (2016).

25.          H. Zhang, Z. Han, W. Song, J. Chai, Structural Insight into Recognition of Plant Peptide Hormones by Receptors. Molecular plant 9, 1454-1463 (2016).

26.          J. Tang, Z. Han, J. Chai, Q&A: what are brassinosteroids and how do they act in plants? BMC biology 14, 113 (2016).

27.          W. Song, L. Liu, J. Wang, Z. Wu, H. Zhang, J. Tang, G. Lin, Y. Wang, X. Wen, W. Li, Z. Han, H. Guo, J. Chai, Signature motif-guided identification of receptors for peptide hormones essential for root meristem growth. Cell research 26, 674-685 (2016).

28.          W. Song, Z. Han, J. Wang, G. Lin, J. Chai, Structural insights into ligand recognition and activation of plant receptor kinases. Current opinion in structural biology 43, 18-27 (2016).

29.          Y. Qiao, B. Zhou, M. Zhang, W. Liu, Z. Han, C. Song, W. Yu, Q. Yang, R. Wang, S. Wang, S. Shi, R. Zhao, J. Chai, J. Chang, A Novel Inhibitor of the Obesity-Related Protein FTO. Biochemistry 55, 1516-1522 (2016).

30.          R. Ma, Z. Han, Z. Hu, G. Lin, X. Gong, H. Zhang, J. B. Nasrallah, J. Chai, Structural basis for specific self-incompatibility response in Brassica. Cell research,  (2016); published online EpubNov 08 (10.1038/cr.2016.129).

31.          S. Liu, J. Wang, Z. Han, X. Gong, H. Zhang, J. Chai, Molecular Mechanism for Fungal Cell Wall Recognition by Rice Chitin Receptor OsCEBiP. Structure (London, England : 1993) 24, 1192-1200 (2016).

32.          J. Wang, W. Wang, W. Song, Z. Han, H. Zhang, J. Chai, H. Wang, J. Wang, An improved method for phasing crystal structures with low non-crystallographic symmetry using cryo-electron microscopy data. Protein & cell 6, 919-923 (2015).

33.          J. Wang, H. Li, Z. Han, H. Zhang, T. Wang, G. Lin, J. Chang, W. Yang, J. Chai, Allosteric receptor activation by the plant peptide hormone phytosulfokine. Nature 525, 265-268 (2015).

34.          J. Tang, Z. Han, Y. Sun, H. Zhang, X. Gong, J. Chai, Structural basis for recognition of an endogenous peptide by the plant receptor kinase PEPR1. Cell research 25, 110-120 (2015).

35.          W. Song, J. Wang, Z. Han, Y. Zhang, H. Zhang, W. Wang, J. Chang, B. Xia, S. Fan, D. Zhang, J. Wang, H. W. Wang, J. Chai, Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13. Nature structural & molecular biology 22, 782-787 (2015).

36.          W. He, B. Zhou, W. Liu, M. Zhang, Z. Shen, Z. Han, Q. Jiang, Q. Yang, C. Song, R. Wang, Identification of a novel small-molecule binding site of the fat mass and obesity associated protein (FTO). Journal of medicinal chemistry 58, 7341-7348 (2015).

37.          W. Song, Z. Han, Y. Sun, J. Chai, Crystal structure of a plant leucine rich repeat protein with two island domains. Science China. Life sciences 57, 137-144 (2014).

38.          Y. Li, L. Zhang, T. Liu, C. Chai, Q. Fang, H. Wu, P. A. Agudelo Garcia, Z. Han, S. Zong, Y. Yu, X. Zhang, M. R. Parthun, J. Chai, R. M. Xu, M. Yang, Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex. Genes & development 28, 1217-1227 (2014).

39.          Z. Han, Y. Sun, J. Chai, Structural insight into the activation of plant receptor kinases. Current opinion in plant biology 20, 55-63 (2014).

40.          B. Zhou, Z. Han, Crystallization and preliminary X-ray diffraction of the RNA demethylase ALKBH5. Acta crystallographica. Section F, Structural biology and crystallization communications 69, 1231-1234 (2013).

41.          Y. Sun, L. Li, A. P. Macho, Z. Han, Z. Hu, C. Zipfel, J. M. Zhou, J. Chai, Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex. Science 342, 624-628 (2013).

42.          Y. Sun, Z. Han, J. Tang, Z. Hu, C. Chai, B. Zhou, J. Chai, Structure reveals that BAK1 as a co-receptor recognizes the BRI1-bound brassinolide. Cell research 23, 1326-1329 (2013).

43.          J. She, Z. Han, B. Zhou, J. Chai, Structural basis for differential recognition of brassinolide by its receptors. Protein & cell 4, 475-482 (2013).

44.          W. Yuan, T. Wu, H. Fu, C. Dai, H. Wu, N. Liu, X. Li, M. Xu, Z. Zhang, T. Niu, Z. Han, J. Chai, X. J. Zhou, S. Gao, B. Zhu, Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science 337, 971-975 (2012).

45.          H. Yang, Z. Han, Y. Cao, D. Fan, H. Li, H. Mo, Y. Feng, L. Liu, Z. Wang, Y. Yue, S. Cui, S. Chen, J. Chai, L. Ma, A companion cell-dominant and developmentally regulated H3K4 demethylase controls flowering time in Arabidopsis via the repression of FLC expression. PLoS genetics 8, e1002664 (2012)10.1371/journal.pgen.1002664).

46.          T. Liu, Z. Liu, C. Song, Y. Hu, Z. Han, J. She, F. Fan, J. Wang, C. Jin, J. Chang, J. M. Zhou, J. Chai, Chitin-induced dimerization activates a plant immune receptor. Science 336, 1160-1164 (2012).

47.          H. Gao, X. Wu, J. Chai, Z. Han, Crystal structure of a TALE protein reveals an extended N-terminal DNA binding region. Cell research 22, 1716-1720 (2012).

48.          J. She, Z. Han, T. W. Kim, J. Wang, W. Cheng, J. Chang, S. Shi, J. Wang, M. Yang, Z. Y. Wang, J. Chai, Structural insight into brassinosteroid perception by BRI1. Nature 474, 472-476 (2011).

49.          D. Shao, X. Zhong, Y. F. Zhou, Z. Han, Y. Lin, Z. Wang, L. Bu, L. Zhang, X. D. Su, H. Wang, Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host. Molecular immunology 47, 726-737 (2010).

50.          Z. Han, T. Niu, J. Chang, X. Lei, M. Zhao, Q. Wang, W. Cheng, J. Wang, Y. Feng, J. Chai, Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464, 1205-1209 (2010).

51.          Z. Han, N. Huang, T. Niu, J. Chai, A loop matters for FTO substrate selection. Protein & cell 1, 616-620 (2010).

52.          D. Shao, Z. Han, Y. Lin, L. Zhang, X. Zhong, M. Feng, Y. Guo, H. Wang, Detection of Plasmodium falciparum derived macrophage migration inhibitory factor homologue in the sera of malaria patients. Acta tropica 106, 9-15 (2008).

53.          Z. Han, X. Xing, M. Hu, Y. Zhang, P. Liu, J. Chai, Structural basis of EZH2 recognition by EED. Structure (London, England : 1993) 15, 1306-1315 (2007).

54.          Z. Han, P. Liu, L. Gu, Y. Zhang, H. Li, S. Chen, J. Chai, Structural basis for histone demethylation by JHDM1. Frontier Science 1, 52-61 (2007).

55.          Z. Han, L. Guo, H. Wang, Y. Shen, X. W. Deng, J. Chai, Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Molecular cell 22, 137-144 (2006).

56.          H. Li, Z. Han, Y. Lu, Y. Lin, L. Zhang, Y. Wu, H. Wang, Isolation and functional characterization of a dynamin-like gene from Plasmodium falciparum. Biochemical and biophysical research communications 320, 664-671 (2004).

57.          Z. Han, D. Shao, H. Wang, Cloning and expression of a homologue of human macrophage migration inhibitory factor from P. falciparum 3D7. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 26, 515-518 (2004).