Structural insights into outer membrane asymmetry maintenance in Gram-negative bacteria by MlaFEDB.
Abstract
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.
References
Structural and Functional Characterization of the LPS Transporter LptDE from Gram-Negative Pathogens
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
ABC Transporters & Multidrug Resistance
ABC Transporters or ATP-Binding Cassette Transporters are responsible for pumping out antibiotics in the cell and can lead to multidrug resistance in bacteria. Discover the latest research on ABC Transporters & Multidrug Resistance here.