姜道华
姜道华
简介:研究员，博士生导师。2009年本科毕业于华中科技大学生物技术系，同年保送本校直博研究生，2010-2014在中国科学院生物物理所联合培养。2014年获理学博士学位。2014年至2020年在美国华盛顿大学（西雅图）从事博士后研究。2020年11月加入中国科学院物理研究所任特聘研究员，2024年任研究员。曾获得国家海外高层次人才引进青年项目、中国科学院引进国外人才计划项目（择优支持），中国科学院优秀导师（2024）等。
jianglab实验室网站：https://www.labxing.com/jianglab-1
主要研究方向:
利用冷冻电镜，X-射线晶体学研究重要膜蛋白结构，结合生化和电生理以及分子动力学模拟研究膜蛋白结构和功能。
过去的主要工作及获得的成果:
长期专注于重要膜蛋白结构和功能的研究。
解析MFS超家族转运蛋白YajR晶体结构，首次展示该家族最保守的结构元件motif A在蛋白转运中发挥稳定外向开口的作用 (PNAS, 2013)。解析首个PP2A家族膜蛋白磷酸水解酶PgpB晶体结构(PNAS, 2014)。
解析携带人类致病突变体的原核电压门控钠通道NavAb晶体结构，提供该突变导致疾病的结构基础 (Nature, 2018)；随后解析了心脏钠离子通道Nav1.5以及通道蛋白结合抗心律不齐药物的冷冻电镜结构，对钠通道激活和失活，离子选择性以及抗心律不齐药物结合位点等提出新的机制 (Cell, 2020; Cell, 2021)。阐明了第一种由N-helix介导的Nav通道快失活机制 (Nat Commun, 2022)，以及Nav通道慢失活机制(Nat Commun, 2024). 小分子和多肽类毒素对离子通道的调控机制(Nat Commun, 2021; Cell reports, 2021; Nat Commun, 2022; NSMB, 2022; Nat Chem Biol, 2023; Nat Commun, 2023; Cell reports, 2023)
解析大脑单胺转运蛋白VMAT2结合不同底物和抑制剂的复合物结构，揭示了药物分子的抑制机制和单胺转运的分子机制(Nature 2024; Cell Research, 2024)。
揭示了SID-1特异性识别dsRNA的结构基础，并提出SID-1介导的系统性RNAi是通过dsRNA内吞作用 (Nat Struct Mol Biol, 2024)。
通过功能和结构分析，揭示了人体唯一磷酸外排蛋白XPR1识别，转运和被信号分子调控的分子机制(Nature 2024)。
近年来，以第一作者或通讯作者在Nature (3), Cell (2), Nature Structural & Molecular Biology (2), Nature Chemical Biology, Cell Research, PNAS (2), Nature Communications (5), Cell Reports (2) 等学术期刊发表论文二十余篇。担任Neuron, Nature Chemical Biology, Nature Communications, Cell Reports, Structure 和European Journal of Medicinal Chemistry等期刊审稿人。
代表性论文及专利:
#为（共同）第一作者，*为（共同）通讯作者
26. Rui Yan#, Huiwen Chen#, Chuanyu Liu#, Jun Zhao#, Di Wu, Juquan Jiang, Jianke Gong, Daohua Jiang*. Human XPR1 structures reveal phosphate export mechanism. Nature 633, 960-967 ( 2024).
25. Di Wu#, Zhuoya Yu#, Qihao Chen#, Jun Zhao#, Bo Huang, Yuhang Wang, Jiawei Su, Na Li, Daohua Jiang*, Yan Zhao*. Structural snapshots of human VMAT2 reveal insights into substrate recognition and proton coupling mechanism. Cell Research. 2024 May, 34, 586-589
24. Huiwen Chen#, Zhanyi Xia#, Jie Dong#, Bo Huang#, Jiangtao Zhang, Feng Zhou, Rui Yan, Yiqiang Shi, Jianke Gong, Juquan Jiang*, Zhuo Huang*, Daohua Jiang*. Structural mechanism of voltage-gated soidum channel slow inactivation. Nature Communications. 2024 May, 15:3691
23. Jiangtao Zhang#, Chunhua Zhan#, Junping Fan#, Dian Wu#, Ruixue Zhang#, Di Wu, Xinyao Chen, Ying Lu, Ming Li, Min Lin, Jianke Gong*, Daohua Jiang*. Structural insights into double-stranded RNA recognition and transport by SID-1. Nature Structural & Molecular Biology. 2024 Apr 25 (Higtlighted by NSMB Research Briefing)
22. Di Wu#, Qihao Chen#, Zhuoya Yu#, Bo Huang#, Jun Zhao#, Yuhang Wang, Jiawei Su, Feng Zhou, Rui Yan, Na Li, Yan Zhao*, Daohua Jiang*. Transport and inhibition mechanisms of human VMAT2. Nature 626, 427-434, 2024 Feb,08
21. Jiangtao Zhang#, Shiqi Liu#, Junping Fan#, Rui Yan#, Bo Huang, Feng Zhou, Tian Yuan, Jianke Gong, Zhuo Huang*, Daohua Jiang*. Structural basis of human Slo2.2 channel gating and modulation. Cell Reports. 2023 Aug, 42, 112858.
20. Yue Li#, Tian Yuan#, Bo Huang#, Feng Zhou, Chao Peng, Xiaojing Li, Yunlong Qiu, Bei Yang, Yan Zhao*, Zhuo Huang*, Daohua Jiang*. Structure of human NaV1. 6 channel reveals Na+ selectivity and pore blockade by 4, 9-anhydro-tetrodotoxin. Nature Communications. 2023 Feb, 14:1030
19. Jiangtao Zhang#, Yiqiang Shi#, Zhuo Huang#, Yue Li, Bei Yang, Jianke Gong, Daohua Jiang*. Structural basis for NaV1.7 inhibition by pore blockers. Nature Structural & Molecular Biology. 2022 Nov,
18. Junping Fan#, Linghan Hu#, Zongwei Yue#, Daohong Liao#, Fusheng Guo, Han Ke, Daohua Jiang*, Yong Yang*, Xiaoguang Lei*. Structural basis of TRPV3 inhibition by an antagonist. Nature Chemical Biology. 2022 Oct,
17. Daohua Jiang*, Jiangtao Zhang, Zhanyi Xia. Structural Advances in Voltage-Gated Sodium Channels. Frontiers in Pharmacology, 2022 Jun, 13:908867 (Review article)
16. Jiangtao Zhang#, Yiqiang Shi#, Junping Fan#, Huiwen Chen#, Zhanyi Xia, Bo Huang, Juquan Jiang, Jianke Gong*, Zhuo Huang*, Daohua Jiang*. N-type fast inactivation of a eukaryotic voltage-gated sodium channel. Nature Communications. 2022 May, 13, 2713
15. Xiaojing Li#, Feng Xu#, Hao Xu#, Shuli Zhang, Yiwei Gao, Hongwei Zhang, Yanli Dong, Yanchun Zheng, Bei Yang, Jianyuan Sun, Xuejun Cai Zhang, Yan Zhao*, Daohua Jiang*. Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist. Nature Communications. 2022 Mar, 13, 1286
14. Yanli Dong#, Yiwei Gao#, Shuai Xu#, Yuhang Wang, Zhuoya Yu, Yue Li, Bin Li, Tian Yuan, Bei Yang, Xuejun Cai Zhang, Daohua Jiang*, Zhuo Huang*, Yan Zhao*. Closed-state inactivation and pore-blocker modulation mechanisms of human CaV2.2. Cell Reports. 2021 Nov 37(5)
13. Daohua Jiang*, Richard Banh, Tamer M Gamal El-Din, Lige Tonggu, Michael J Lenaeus, Régis Pomès, Ning Zheng*, William A Catterall*. Open-state structure and pore gating mechanism of the cardiac sodium channel. Cell. 2021, 184(20) (News story describing this work was highlighted in Nat Struct Mol Biol 28, 777 (2021))
12. Jiang D., Tonggu L., Gamal El-Din, Banh R., P.,Pomes, Zheng N.*, Catterall W.A.* Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin. Nature Communications. 2021 12(1)
11. D Jiang, TG El-Din, N Zheng, WA Catterall*. Expression and purification of the cardiac sodium channel NaV1. 5 for cryo-EM structure determination. Methods in Enzymology 2021 653, 89-101
2020年回国前：
10. Xu C., Lu P, Gamal El-Din, Pei X. Y., Johnson M. C., Uyeda A., Bick M. J., Xu Q., Jiang D., Bai H., Reggiano G., Hsia Y., Brunette TJ, Dou J., Ma D., Lynch E. M., E Boyken S., Huang P., L. Stewart, DiMaio F., Kollman J. M., Luisi B. F., Matsuura T., Catterall W.A., Baker D. Computational design of transmembrane pores. Nature 2020 Sep. 585(7823), 129-134
9. Jiang, D.#, Shi, H.#, Tonggu, L., Gamal El-Din, Zheng, Leneaus, M.J., Zhao, Y., Yoshiaki, C., Zheng,N., Catterall, W.A. Structure of the Cardiac Sodium Channel. Cell, Volume 180, Issue 1, 9 January 2020, Pages 122-134.e10
8. Jiang, D.#, Gamal El-Din#, T.M.,Ing, C.,Lu, P.,Pomes, R.,Zheng, N.,Catterall, W.A. Structural basis for gating pore current in periodic paralysis. Nature. 2018 May. DOI:10.1038/s41586-018-0120-4
7. XC. Zhang, Y. Zhao, J. Heng, D. Jiang Energy coupling mechanisms of MFS transporters. Protein Science. 2015; 24 (10), 1560-1579
6. Daohua Jiang#, Yan Zhao#, Junping Fan, Xuehui Liu, Yan Wu, Wei Feng, Xuejun C Zhang*. Atomic resolution structure of the E. coli YajR transporter YAM domain. Biochemical and Biophysical Research Communications 2014 Jul; 450(2):929-935
5. Fan J#, Jiang D#, Zhao Y, Liu J, Zhang XC. Crystal Structure of Lipid Phosphatase E. coli PgpB. Proc Natl Acad Sci U S A. 2014 May;111(21):7636-40.
4. XC Zhang, J Liu, D Jiang Why is dimerization essential for class-C GPCR function? New insights from mGluR1 crystal structure analysis. Protein & cell 2014; 5 (7), 492-495
3. Xusheng Kang, Yan Zhao, Daohua Jiang, Xuemei Li, Xianping Wang, Yan Wu, Zeliang Chen, Xuejun C Zhang. Crystal structure and biochemical studies of Brucella melitensis 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Biochemical and Biophysical Research Communications 2014 Apr; 446(4):965-970
2. Jiang D#, Zhao Y#, Wang X#, Fan J, Heng J, Liu X, Feng W, Kang X, Huang B, Liu J, Zhang XC. Structure of the YajR transporter suggests a transport mechanism based on the conserved motif A. Proc Natl Acad Sci U S A. 2013 Sep;110(36):14664-9.
1. Jiang D#, Fan J#, Wang X, Zhao Y, Huang B, Liu J, Zhang XC. Crystal structure of 1,3Gal43A, an exo-β-1,3-galactanase from Clostridium thermocellum. J Struct Biol. 2012 Dec;180(3):447-57.
目前的研究课题及展望:
跨膜蛋白是一类包埋其疏水部分于生物膜的蛋白质，主要发挥跨细胞膜的物质运输、能量代谢、信号转导和生物膜系统稳态等多种功能。在人类基因组中，大约30%的基因编码的蛋白质被认为是膜蛋白，而目前在权威蛋白质结构数据库（Protein Databank, PDB）中，膜蛋白结构仅占2%左右，表明对膜蛋白的结构研究相对滞后。然而，大约70% FDA-approved药物的作用靶点是膜蛋白。研究膜蛋白结构可以为以结构为基础的药物设计提供模板。
本实验室利用物理所冷冻电镜平台（一台Titan 300kV + K3 camera，一台glacios 200kV + K3 camera), 研究在生命活动中发挥重要功能的膜蛋白结构，争取获得同一膜蛋白不同构象以及膜蛋白复合物结构，以便更好的理解膜蛋白如何发挥功能。
培养研究生情况:
每年招收博士研究生1-3名。热忱欢迎各学科（生物、化学或物理）背景的学生加入。
同时非常欢迎联合培养研究生来实验室做研究（长期有效）。
招聘博士后，研究助理。
其他联系方式:
Email: jiangdh@iphy.ac.cn
Email:
jiangdh@iphy.ac.cn