细菌外膜
大肠杆菌
细菌
膜
肽聚糖
周质间隙
生物
内膜
单元格信封
细菌细胞结构
磷脂
细胞生物学
微生物学
生物物理学
跨膜蛋白
膜蛋白
化学
生物化学
外膜外排蛋白
革兰氏阳性菌
作者
Xiaodi Tang,Shenghai Chang,Wen Qiao,Qinghua Luo,Yuejia Chen,Zhiying Jia,James Coleman,Ke Zhang,Ting Wang,Zhibo Zhang,Changbin Zhang,Xiaofeng Zhu,Xiawei Wei,Changjiang Dong,Xing Zhang,Haohao Dong
标识
DOI:10.1038/s41594-020-00532-y
摘要
The highly asymmetric outer membrane of Gram-negative bacteria functions in the defense against cytotoxic substances, such as antibiotics. The Mla pathway maintains outer membrane lipid asymmetry by transporting phospholipids between the inner and outer membranes. It comprises six Mla proteins, MlaFEDBCA, including the ABC transporter MlaFEDB, which functions via an unknown mechanism. Here we determine cryo-EM structures of Escherichia coli MlaFEDB in an apo state and bound to phospholipid, ADP or AMP-PNP to a resolution of 3.3-4.1 Å and establish a proteoliposome-based transport system that includes MlaFEDB, MlaC and MlaA-OmpF to monitor the transport direction of phospholipids. In vitro transport assays and in vivo membrane permeability assays combined with mutagenesis identify functional residues that not only recognize and transport phospholipids but also regulate the activity and structural stability of the MlaFEDB complex. Our results provide mechanistic insights into the Mla pathway, which could aid antimicrobial drug development.
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