生物大分子重点实验室

1999 - 2003 北京大学物理学院，物理学学士

2003 - 2008 北京大学物理学院，理学博士

2008 - 2014 美国普渡大学结构生物系，Post-doctoral research associate

2014 - 至今 中科院生物物理研究所，研究员，博士生导师

1. 发展冷冻电子显微术方法

发展冷冻电子显微术，提高对病毒和蛋白质复合物三维重构的分辨率；推广冷冻电子显微术的应用范围。

2. 利用冷冻电子显微术研究重要蛋白质复合物的结构及功能

随着冷冻电子显微术的发展，电子显微镜在研究生物样品的结构方面起到了越来越重要的作用。通过利用冷冻电子显微术获得的高分辨率(~3.5 angstrom)的蛋白质结构，能十分有效的帮助了解这些蛋白质的结构和功能之间的联系。近年来，冷冻电子显微术硬件技术(包括直接电子探头，相位板等)的发展，大大提高了电子显微镜数据的质量。随着这些技术的应用，使得能够获得高分辨三维结构的生物样品的大小从10⁶~10⁸道尔顿(传统样品病毒)延伸至10⁵道尔顿(大蛋白及一般蛋白质复合物)，大大扩展了高分辨冷冻电镜的研究范围。本研究组利用冷冻电子显微术，在生理条件下，对具有重要生物功能的蛋白质大分子的结构进行高分辨三维重构，从准原子分辨率的结构上了解蛋白质复合体的机制和功能。

3. 利用冷冻电子显微术研究病毒的三维结构及病毒入侵、感染细胞以及抗体中和病毒的机制

利用单颗粒冷冻电子显微术在准原子分辨率(<4 angstrom)的基础上对病毒的结构蛋白进行研究。研究对象包括研究病毒的蛋白质外壳层以及这个蛋白质外壳层在感染宿主细胞过程中可能存在的多种状态的三维结构，这些研究也会关注病毒的蛋白质外壳层在细胞内自组装时处于中间态时的结构。在病毒生命周期的不同状态下的病毒颗粒可以通过提纯直接得到或者通过对病毒周围环境的体外模拟得到。 这些研究可以将所得到的结构信息与功能相对应，从而可以在准原子分辨率的基础上理解病毒侵染细胞和在细胞内自组装的机制。

1. Cao DF^#, Ma BT^#, Cao ZY^#, Zhang XZ*, Xiang Y*. Structure of Semliki Forest virus in complex with its receptor VLDLR. Cell, 2023,186(10):2208-2218.e15.

2. Cheng J^#, Liu T^#, You X, Zhang F, Sui SF, Wan XH*, Zhang XZ*. Determining protein structures in cellular lamella at pseudo-atomic resolution by GisSPA. Nature Communications, 2023, 14(1):1282.

3. You X^#, Zhang X^#, Cheng J^#, Xiao YN^#, Ma JF, Sun S, Zhang XZ*, Wang HW* & Sui SF*. In situ structure of the red algal phycobilisome-PSII-PSI-LHC megacomplex. Nature, 2023, 616(7955):199-206.

4. Shi HG^#, Wu CL^#, Zhang XZ. Addressing compressive deformation of proteins embedded in crystalline ice. Structure, 2023, 31(2):213-220.e3.

5. Wang M^#, Sun ZZ ^#, Cui CX^#, Wang SD, Yang DC, Shi ZB, Wei XY, Wang PF, Sun WY, Zhu J, Li JQ, Du BC, Liu ZS, Wei LL, Liu CG, He XJ, Wang XX*, Zhang XZ*, Wang JF*. Structural Insights into Alphavirus Assembly Revealed by the Cryo-EM Structure of Getah Virus. Viruses, 2022, 14(2):327.

6. Zhu DJ, Shi HG, Wu CL & Zhang XZ. An electron counting algorithm improves imaging of proteins with low-acceleration-voltage cryoelectron microscope. Communications Biology, 2022, 5(1):321.

7. Su XD^#, Cao DF^#, Pan XW*, Shi, LF, Liu ZF, Dall'Osto L, Bassi R, Zhang XZ* and Mei Li*. Supramolecular assembly of chloroplast NADH dehydrogenase-like complex with photosystem I from Arabidopsis thaliana. Molecular Plant, 2022, 15, 454-467.

8. Ma J ^#, Zhang SY^# & Zhang XZ. Structure of Machupo virus polymerase in complex with matrix protein Z. Nature Communications, 2021; 12: 6163.

9. Ma BT^#, Huang CQ^#, Ma J^#, Xiang Y* & Zhang XZ*. Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3. Nature, 2021, 598(7882): 677-681.

10. Cheng J, Li BF, Si L, Zhang XZ. Determining structures in a native environment using single-particle cryo-electron microscopy images. The Innovation. 2021, 2(4): 100166.

11. Wu CL^#, Shi HG^#, Zhu DJ, Fan KL, Zhang XZ. Low-cooling-rate freezing in biomolecular cryo-electron microscopy for recovery of initial frames. QRB Discovery. 2021: e11.

12. Li BF, Zhu DJ, Shi HG, Zhang XZ. Effect of charge on protein preferred orientation at the air-water interface in cryo-electron microscopy. Journal of Structural Biology, 2021, 213(4): 107783.

13. Cheng J, Zhang XZ. Optimizing weighting functions for cryo-electron microscopy. Biophysics Reports. 2021, 7 (2), 152-158.

14. Song GT^#, Xu BJ^#, Shi HG^#, Zhang Y, Zhang DJ, Cao XT, Liu ZR, Guo R, Guan YZ, Chu YH, Zhang XZ*, Lou JZ*, Qin Y*. Conformational activation of ribosome recycling by intra- and inter-molecular dynamics of RRF. International Journal of Biological Macromolecules, 2020, 160: 1212-1219.

15. Xu X^#, Shi HG ^#, Gong XW, Chen P, Gao Y, Zhang XZ*, Xiang S*. Structural insights into sodium transport by the oxaloacetate decarboxylase sodium pump. eLife, 2020, 9 :e53853.

16. Zhang MF^#, Shi HG^#, Zhang XM^#, Zhang XZ*, Huang YH*. Cryo-EM structure of the nonameric CsgG-CsgF complex and its implications for controlling curli biogenesis in Enterobacteriaceae. PLoS Biology, 2020, 18(6): e3000748.

17. Fan XY^#, Cao DF^#*, Kong LF, Zhang XZ*. Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein. Nature Communications, 2020, 11(1): 3618.

18. Cao DF^#, Han XN^#, Fan XY^#, Xu RM*, Zhang XZ*. Structural basis for nucleosome-mediated inhibition of cGAS activity. Cell Research, 2020.

19. Gao YN^#, Cao DF^#, Zhu JP, Feng H, Luo X, Liu SQ, Yan XX, Zhang XZ*, Gao P*. Structural insights into assembly, operation and inhibition of a type I restriction-modification system. Nature Microbiology, 2020, 5(9): 1107-1118.

20. Pan XW^#, Cao DF^#, Xie F^#, Xu F^#, Su XD, Mi HL*, Zhang XZ*, Li M*. Structural basis for electron transport mechanism of complex I-like photosynthetic NAD(P)H dehydrogenase. Nature Communications, 2020, 11(1): 610.

21. Cao P^#, Cao D^#, Si L, Su XD, Tian LJ, Chang WR, Liu ZF, Zhang XZ*, Li M*. Structural basis for energy and electron transfer of the photosystem I-IsiA-flavodoxin supercomplex. Nature Plants, 2020, 6(2): 167-176.

22. Liu S^#, Luo YZ^#, Wang YJ^#, Li SH^#, Zhao Z, Bi YH, Sun JQ, Peng RC, Song H, Zhu DJ, Sun Y, Li S, Zhang L, Wang W, Sun YP, Qi JX, Yan JH, Shi Y *, Zhang XZ*, Wang PY*, Qiu HJ* and Gao GF*. Cryo-EM Structure of the African Swine Fever Virus. Cell Host & Microbe, 2019, 26(6): 836-843 e833.

23. Wu CL^#, Huang XJ^#, Cheng J, Zhu DJ, Zhang XZ. High-quality, high-throughput cryo-electron microscopy data collection via beam tilt and astigmatism-free beam-image shift. Journal of Structural Biology,2019.

24. Su XD^#, Ma J^#, Pan XW^#, Zhao XL, Chang WR, Liu ZF, Zhang XZ* and Li M*. Antenna arrangement and energy transfer pathways of a green algal photosystem-I-LHCI supercomplex. Nature Plants, 2019, 5(3): 273-281.

25. You L^#, Ma J^#, Wang J^#, Artamonova D, Wang M, Liu L, Artamonova D, Wang M, Liu L, Xiang H, Severinov K. Zhang XZ* and Wang YL*. Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference. Cell, 2019, 176(1-2): 239-253 e216.

26. Fang QL^#, Zhu DJ^#, Agarkova I, Adhikari J, Klose T, Liu Y, Chen ZG, Sun YY, Michael L. Gross, Van Etten J, Zhang XZ* & Rossmann MG*. Near-atomic structure of a giant virus. Nature Communications, 2019, 10(1): 388.

27. Pan XW^#, Ma J^#, Su XD^#, Cao P, Chang W, Liu ZF, Zhang XZ*, Li M*. Structure of the maize photosystem I supercomplex with light-harvesting complexes I and II. Science, 2018, 360(6393): 1109-1113.

28. Wang JL^#, Yuan S^#, Zhu DJ^#, Tang H, Wang N, Chen WY, Gao Q, Li YH, Wang JZ, Liu HR*, Zhang XZ*, Rao ZH*, Wang XX*. Structure of the herpes simplex virus type 2 C-capsid with capsid-vertex-specific component. Nature Communications, 2018, 9(1): 3668.

29. Yuan S^#, Wang JL^#, Zhu DJ^#, Wang N, Gao Q, Chen WY, Tang H, Wang JZ*, Zhang XZ*, Liu HR*, Rao ZH*, Wang XX*. Cryo-EM structure of a herpesvirus capsid at 3.1 Å. Science, 2018, 360(6384).

30. Zhu DJ, Wang XX, Fang QL, Van Etten JL, Rossmann MG, Rao ZH, Zhang XZ. Pushing the resolution limit by correcting the Ewald sphere effect in single-particle Cryo-EM reconstructions. Nature Communications, 2018, 9(1): 1552.

31. Chen LH^#, Wang M^#, Zhu DJ^#, Sun ZH^#, Ma J, Wang JL, Kong LF, Wang SD, Liu ZS, Wei LL, He YW, Wang JF*, Zhang XZ*. Implication for alphavirus host-cell entry and assembly indicated by a 3.5 Å resolution cryo-EM structure. Nature Communications, 2018, 9(1): 5326.　　

32. Yuan Y^#, Cao DF^#, Zhang YF^#, Ma J^#, Qi JX, Wang QH, Lu GW, Wu Y, Yan JH, Shi Y*, Zhang XZ* & Gao GF*. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains, Nature Communications, 2017, 8:15092.

33. Liu L^#, Li XY^#, Ma J^#, Li ZQ^#, You LL, Wang JY, Wang M, Zhang XZ*, Wang YL*. The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a. Cell, 2017, 170(4):714-726.e10.　　

34. Su XD^#, Ma J^#, Wei XP^#, Cao P^#, Zhu DJ, Chang WR, Liu ZF*, Zhang XZ*, Li M*. Structure and assembly mechanism of plant C2S2M2-type PSII-LHCII supercomplex. Science, 2017, 357 (6353): 815-820.

35. Wei XP^#, Su XD^#, Cao P, Liu XY, Chang WR, Li M*, Zhang XZ*, Liu ZF*. Structure of spinach photosystem II-LHCII supercomplex at 3.2 Å resolution. Nature, 2016; 534(7605):69-74.

36. Wang JY^#, Ma J^#, Cheng Z, Meng X, You LL, Wang M, Zhang XZ*, Wang YL*. A CRISPR evolutionary arms race: structural insights into viral anti-CRISPR/Cas responses. Cell Research, 2016, 26:1165-1168.

37. Sun L^#, Zhang XZ^#, Gao S^#, Rao PA, Padilla-Sanchez V, Chen ZG, SunSY, Xiang Y, Subramaniam S, Rao VB*, and Rossmann MG*. Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution. Nature Communications, 2015, 6: 7548.

38. Zhang XZ, Sheng J, Austin SK, Hoornweg TE, Smit JM, Kuhn RJ, Diamond MS, and Rossmann MG. Structure of acidic pH dengue virus showing the fusogenic glycoprotein trimers. Journal of Virology, 2015, 89: 743-750.

39. Sun L^#, Young LN^#, Zhang XZ^#, Boudko SP, Fokine A, Zbornik E, Roznowski AP, Molineux IJ, Rossmann MG* and Fane BA*.Icosahedral bacteriophage PhiX174 forms a tail for DNA transport during infection. Nature, 2014, 505: 432-435.

40. Zhang XZ, Sheng J, Plevka P, Kuhn RJ, Diamond MS, and Rossmann MG. Dengue structure differs at the temperatures of its human and mosquito hosts. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110: 6795-6799.

Highlighted by Nature (May 23, 2013, 497 7450 443-444), Cell (May 9, 2013, 153 4 727-729) and Nature Structural & Molecular Biology (May 6, 2013, 20 546)

41. Zhang XZ, Sun SY, Xiang Y, Wong J, Klose T, Raoult D, and Rossmann MG. Structure of Sputnik, a virophage, at 3.5 Å resolution. Proceedings of the National Academy of Sciences of the United States of America,2012, 109:18431-18436.

42. Zhang XZ, Xiang Y, Dunigan DD, Klose T, Chipman PR, Van Etten JL, and Rossmann MG. Three-dimensional structure and function of the Paramecium bursaria chlorella virus capsid. Proceedings of the National Academy of Sciences of the United States of America, 2011,108:14837-14842.

（资料来源：章新政研究员，2024-05-16）