Structure of bacterial phospholipid transporter MlaFEDB with substrate bound
- New York University School of Medicine, United States
Abstract
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 remains 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.
Data availability
The model has been deposited in PDB under the accession code 6XBD and the map has been deposited in EMDB under the accession code EMD-22116. Raw data were deposited into EMPIAR (EMPIAR-10536).Plasmids generated in this study will be deposited in Addgene.
Article and author information
Author details
Funding
National Institutes of Health (R35GM128777)
- Damian C Ekiert
National Institutes of Health (R00GM112982)
- Gira Bhabha
Damon Runyon Cancer Research Foundation (DFS-20-16)
- Gira Bhabha
Pew Charitable Trusts (PEW-00033055)
- Gira Bhabha
American Heart Association (20POST35210202)
- Georgia L Isom
National Institutes of Health (T32 GM088118)
- Mark R MacRae
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Adam Frost, University of California, San Francisco, United States
Version history
- Received: August 27, 2020
- Accepted: November 24, 2020
- Accepted Manuscript published: November 25, 2020 (version 1)
- Version of Record published: January 7, 2021 (version 2)
Copyright
© 2020, Coudray et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure of bacterial phospholipid transporter MlaFEDB with substrate bound
eLife 9:e62518.
https://doi.org/10.7554/eLife.62518
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