Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.
Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.
复制标题
DOI：
10.1038/nmicrobiol.2017.70
复制
发表时间：
2017-05-15
影响因子：
28.3
通讯作者：
Du D
中科院分区：
文献类型：
--
作者：
Fitzpatrick AWP;Llabrés S;Neuberger A;Blaza JN;Bai XC;Okada U;Murakami S;van Veen HW;Zachariae U;Scheres SHW;Luisi BF;Du D
大肠杆菌的MACA-MACB-TolC组件是一种跨膜机，它跨越细胞膜并主动挤出底物，包括大环内酯类抗生素和多肽毒力因子。这些转运过程由ATP结合盒(ABC)超家族的成员ATPase MacB提供能量。我们提出了一种近原子分辨率的ABC型三体组装的电子冷冻显微镜结构。周质蛋白MacA的六角体连接在外膜的TolC三聚体和内膜的MacB二聚体之间，形成具有底物转运中心通道的四元结构。在MACA中发现的门环被认为是衬底传输中的单向阀。MacB结构具有一个非典型的跨膜结构域(TMD)，具有紧密堆积的二聚体界面和一个周质开口，可能是底物从周质进入的门户，随后通过变构运输机制进行移位。
The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA is proposed to act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain (TMD) with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism.