南方科技大学知识苑(SUSTech KC): Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition

题名	Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition
作者	Wang，Shuhui 1,10; Wang，Kun 1,2; Song，Kangkang 3,4; Lai，Zon Weng 2,11; Li，Pengfei 5; Li，Dongying1,12 ; Sun，Yajie 6; Mei，Ye 7; Xu，Chen 3,4; Liao，Maofu8,9
通讯作者	Wang，Shuhui; Liao，Maofu
发表日期	2024-09-04
DOI	10.1038/s41467-024-51948-9
发表期刊	Nature Communications 影响因子和分区
EISSN	2041-1723
卷号	15 期号:1
摘要	As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
学校署名	通讯
Scopus记录号	2-s2.0-85203292915
来源库	Scopus
引用统计
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/828690
专题	生命科学学院_化学生物学系南方科技大学生命科学学院冷冻电镜中心
作者单位	1.Department of Cell Biology,Harvard Medical School,Boston,United States 2.Department of Molecular Metabolism,Harvard T.H. Chan School of Public Health,Boston,United States 3.Department of Biochemistry & amp; Molecular Biotechnology,University of Massachusetts Chan Medical School,Worcester,United States 4.Cryo-EM Core Facility,University of Massachusetts Chan Medical School,Worcester,United States 5.Single Particle,LLC,San Diego,United States 6.Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China 7.State Key Laboratory of Precision Spectroscopy,School of Physics and Electronic Science,East China Normal University,Shanghai,China 8.Department of Chemical Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,China 9.Institute for Biological Electron Microscopy,Southern University of Science and Technology,Shenzhen,China 10.Department of Molecular Biophysics and Biochemistry,Yale University,New Haven,United States 11.mRNA Center of Excellence,Sanofi,Waltham,United States 12.Cryo-electron microscopy center,Southern University of Science and Technology,Shenzhen,China
通讯作者单位	化学生物学系; 生命科学学院; 南方科技大学
推荐引用方式 GB/T 7714	Wang，Shuhui,Wang，Kun,Song，Kangkang,et al. Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition[J]. Nature Communications,2024,15(1).
APA	Wang，Shuhui.,Wang，Kun.,Song，Kangkang.,Lai，Zon Weng.,Li，Pengfei.,...&Liao，Maofu.(2024).Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.Nature Communications,15(1).
MLA	Wang，Shuhui,et al."Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition".Nature Communications 15.1(2024).