In situ structure and assembly of the multidrug efflux pump AcrAB-TolC

doi:10.1038/s41467-019-10512-6

	In situ structure and assembly of the multidrug efflux pump AcrAB-TolC
	Shi, Xiaodong 1,2,3; Chen, Muyuan 1; Yu, Zhili 1; Bell, James M.1,4; Wang, Hans 1; Forrester, Isaac 5; Villarreal, Heather 5; Jakana, Joanita 5; Du, Dijun6,8 ; Luisi, Ben F.6; Ludtke, Steven J.1; Wang, Zhao 1,7
	2019-06-14
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	10
发表状态	已发表
DOI	10.1038/s41467-019-10512-6
摘要	Multidrug efflux pumps actively expel a wide range of toxic substrates from the cell and play a major role in intrinsic and acquired drug resistance. In Gram-negative bacteria, these pumps form tripartite assemblies that span the cell envelope. However, the in situ structure and assembly mechanism of multidrug efflux pumps remain unknown. Here we report the in situ structure of the Escherichia coli AcrAB-TolC multidrug efflux pump obtained by electron cryotomography and subtomogram averaging. The fully assembled efflux pump is observed in a closed state under conditions of antibiotic challenge and in an open state in the presence of AcrB inhibitor. We also observe intermediate AcrAB complexes without TolC and discover that AcrA contacts the peptidoglycan layer of the periplasm. Our data point to a sequential assembly process in living bacteria, beginning with formation of the AcrAB subcomplex and suggest domains to target with efflux pump inhibitors.
收录类别	SCI ; SCIE
语种	英语
资助项目	NIH[R01GM080139] ; NIH[P01GM121203]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000471586700012
出版者	NATURE PUBLISHING GROUP
WOS关键词	CRYSTAL-STRUCTURE ; ANTIBIOTIC-RESISTANCE ; TRANSPORTER ; SUGGESTS ; COMPLEX ; SYSTEM
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/48964
专题	生命科学与技术学院_PI研究组_杜迪军组
通讯作者	Wang, Zhao
作者单位	1.Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA 2.Xuzhou Med Univ, Jiangsu Prov Key Lab Anesthesiol, Xuzhou 221004, Jiangsu, Peoples R China 3.Xuzhou Med Univ, Jiangsu Prov Key Lab Anesthesia & Analgesia Appli, Xuzhou 221004, Jiangsu, Peoples R China 4.Baylor Coll Med, Grad Program Quantitat & Computat Biosci, Houston, TX 77030 USA 5.Baylor Coll Med, CryoEM Core, Houston, TX 77030 USA 6.Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England 7.Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Shi, Xiaodong,Chen, Muyuan,Yu, Zhili,et al. In situ structure and assembly of the multidrug efflux pump AcrAB-TolC[J]. NATURE COMMUNICATIONS,2019,10.
APA	Shi, Xiaodong.,Chen, Muyuan.,Yu, Zhili.,Bell, James M..,Wang, Hans.,...&Wang, Zhao.(2019).In situ structure and assembly of the multidrug efflux pump AcrAB-TolC.NATURE COMMUNICATIONS,10.
MLA	Shi, Xiaodong,et al."In situ structure and assembly of the multidrug efflux pump AcrAB-TolC".NATURE COMMUNICATIONS 10(2019).