研究内容:
课题组主要从事疾病相关蛋白质机器的结构与功能研究。目前聚焦于结核分枝杆菌重要生理过程中的膜蛋白及其复合物研究,具体内容包括:
1. 分泌系统复合物机器组成、组装、分泌和调控机制研究
2. 转运系统膜蛋白结构和功能机制、药物外排机制研究
3. 以关键蛋白靶点的结构为指导,开展新药设计与开发
课题组网站:
1.
解析分枝杆菌关键药靶蛋白
MmpL3
多个
“
药靶
&
药物
”
复合物的三维结构,揭示临床药物
SQ109
等创新药物杀死结核菌的全新分子机制
,并开发出新型抗结核小分子
(
Cell 2019
)
。
2.
解析一线抗结核药物乙胺丁醇靶点
EmbA-EmbB
复合物和
EmbC
2
复合物的一系列结构,揭示乙胺丁醇靶向
Emb
蛋白的精确作用机制(
Science 2020
)。
3.
解析临床药物
Q203
靶点
——
呼吸链超级复合体
CIII
2
CIV
2
SOD
2
的冷冻电镜结构,揭示能量代谢过程中电子传递和自由基清除全新机制(
Science 2018
)。
4.
解析毒力因子
Rv0222
结构,结合功能研究发现结核分枝杆菌利用宿主泛素化系统抵御宿主攻击的免疫逃逸新机制(
Nature 2020
)。
5.
解析异烟肼诱导蛋白
IniA
结构,结合功能研究发现
IniA
属于细菌型类动力蛋白家族并参与膜分裂过程,提出膜修复引起药物耐受的模型(
Nature Communications 2019
)。
1.
Chen Zhu*; Yanfeng Shi; Jing Yu; Wenhao Zhao; Lingqiao Li; Jingxi Liang; Xiaolin Yang; Bing Zhang; Yao Zhao; Yan Gao; Xiaobo Chen; Xiuna Yang; Lu Zhang; Luke W. Guddat; Lei Liu; Haitao Yang
#
; Zihe Rao
#
; Jun Li
#
.
Cryo-EM structures of a prokaryotic heme transporter CydDC.
PROTEIN & CELL
. 5 May 2023.
2.
Wang, Haofeng*; Xiao, Yunjie; Chen, Xia; Zhang, Mengwen; Sun, Guangxin; Wang, Feng; Wang, Lin; Zhang, Hanxiao; Zhang, Xiaoyu; Yang, Xin; Li, Wenling; Wei, Yi; Yao, Deqiang; Zhang, Bing; Li, Jun; Cui, Wen; Wang, Fenghua; Chen, Cheng; Shen, Wei; Su, Dan; Bai, Fang; Huang, Jinhai; Ye, Sheng; Zhang, Lei; Ji, Xiaoyun; Wang, Wei
#
; Wang, Zefang
#
; Hochstrasser, Mark
#
; Yang, Haitao
#
.
Crystal Structures of Wolbachia CidA and CidB Reveal Determinants of Bacteria-induced Cytoplasmic Incompatibility and Rescue.
NATURE COMMUNICATIONS
. 25 Mar 2022. 13(1):1608.
3.
Zhang, Lu*; Zhao, Yao*; Gao, Yan; Wu, Lijie; Gao, Ruogu; Zhang, Qi; Wang, Yinan; Wu, Chengyao; Wu, Fangyu; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Zhao, Wei; Qin, Ling; Yang, Xiuna; Wang, Manfu; Zhu, Yan; Zhang, Bing; Bi, Lijun; Zhang, Xian'en; Yang, Haitao; Guddat, Luke W.; Xu, Wenqing; Wang, Quan
#
; Li, Jun
#
; Besra, Gurdyal S.
#
; Rao, Zihe
#
.
Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.
SCIENCE
. 12 Jun 2020. 368(6496):1211.
4.
Gao, Yan*; Yan, Liming*; Huang, Yucen*; Liu, Fengjiang*; Zhao, Yao; Cao, Lin; Wang, Tao; Sun, Qianqian; Ming, Zhenhua; Zhang, Lianqi; Ge, Ji; Zheng, Litao; Zhang, Ying; Wang, Haofeng; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Hua, Tian; Zhang, Bing; Yang, Xiuna; Li, Jun; Yang, Haitao; Liu, Zhijie; Xu, Wenqing; Guddat, Luke W.; Wang, Quan
#
; Lou, Zhiyong
#
; Rao, Zihe
#
.
Structure of the RNA-dependent RNA polymerase from COVID-19 virus.
SCIENCE
. 15 May 2020. 368(6492):779-+.
5.
Zhang, Lu*; Zhao, Yao*; Gao, Ruogu*; Li, Jun; Yang, Xiuna; Gao, Yan; Zhao, Wei; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Besra, Kajelle Kaur; Xu, Wenqing; Bi, Lijun; Zhang, Xian'en; Guddat, Luke W.; Yang, Haitao; Wang, Quan
#
; Besra, Gurdyal S.
#
; Rao, Zihe
#
.
Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB(2)-AcpM(2).
PROTEIN & CELL
. 03 May 2020. 11(7):505-517.
6.
Wang, Lin*; Wu, Juehui*; Li, Jun*; Yang, Hua; Tang, Tianqi; Liang, Haijiao; Zuo, Mianyong; Wang, Jie; Liu, Haipeng; Liu, Feng; Chen, Jianxia; Liu, Zhonghua; Wang, Yang; Peng, Cheng; Wu, Xiangyang; Zheng, Ruijuan; Huang, Xiaochen; Ran, Yajun; Rao, Zihe
#
; Ge, Baoxue
#
.
Host-mediated ubiquitination of a mycobacterial protein suppresses immunity.
NATURE
. 30 Jan 2020. 577(7792):682-+.
9.
Zhang, Bing*; Li, Jun
#
*; Yang, Xiaolin; Wu, Lijie; Zhang, Jia; Yang, Yang; Zhao, Yao; Zhang, Lu; Yang, Xiuna; Yang, Xiaobao; Cheng, Xi; Liu, Zhijie; Jiang, Biao; Jiang, Hualiang; Guddat, Luke W.; Yang, Haitao
#
; Rao, Zihe
#
.
Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target.
CELL
. 24 Jan 2019. 176(3):636-+.
10.
Gong, Hongri*; Li, Jun*; Xu, Ao*; Tang, Yanting; Ji, Wenxin; Gao, Ruogu; Wang, Shuhui; Yu, Lu; Tian, Changlin; Li, Jingwen; Yen, Hsin-Yung; Lam, Sin Man; Shui, Guanghou; Yang, Xiuna; Sun, Yuna; Li, Xuemei; Jia, Minze; Yang, Cheng; Jiang, Biao; Lou, Zhiyong; Robinson, Carol V.; Wong, Luet-Lok; Guddat, Luke W.; Sun, Fei
#
; Wang, Quan
#
; Rao, Zihe
#
.
An electron transfer path connects subunits of a mycobacterial respiratory supercomplex.
SCIENCE
. 30 Nov 2018. 362(6418):1020-+.
11.
Zhang, Jia*; Zhang, Bing; Zhao, Yao; Yang, Xiuna; Huang, Min; Cui, Peng; Zhang, Wenhong; Li, Jun
#
; Zhang, Ying
#
.
Snapshots of catalysis: Structure of covalently bound substrate trapped in Mycobacterium tuberculosis thiazole synthase (ThiG).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
. 26 Feb 2018. 497(1):214-219.
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