Structure of bacterial phospholipid transporter MlaFEDB with substrate bound

Nicolas Coudray, Georgia L Isom, Mark R MacRae, Mariyah N Saiduddin, Gira Bhabha, Damian C Ekiert
2020 eLife  
In double-membraned bacteria, phospholipid transport across the cell envelope is critical to maintain the outer membrane barrier, which plays a key role in virulence and antibiotic resistance. An MCE transport system called Mla has been implicated in phospholipid trafficking and outer membrane integrity, and includes an ABC transporter, MlaFEDB. The transmembrane subunit, MlaE, has minimal sequence similarity to other transporters, and the structure of the entire inner-membrane MlaFEDB complex
more » ... emains unknown. Here we report the cryo-EM structure of MlaFEDB at 3.05 Å resolution, revealing distant relationships to the LPS and MacAB transporters, as well as the eukaryotic ABCA/ABCG families. A continuous transport pathway extends from the MlaE substrate-binding site, through the channel of MlaD, and into the periplasm. Unexpectedly, two phospholipids are bound to MlaFEDB, suggesting that multiple lipid substrates may be transported each cycle. Our structure provides mechanistic insight into substrate recognition and transport by MlaFEDB.
doi:10.7554/elife.62518 pmid:33236984 pmcid:PMC7790496 fatcat:ere64lnax5e5xohceutyfpx3xy