Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation
Abstract
ABC transporters facilitate the movement of diverse molecules across cellular membranes, but how their activity is regulated post-translationally is not well understood. Here we report the crystal structure of MlaFB from E. coli, the cytoplasmic portion of the larger MlaFEDB ABC transporter complex, which drives phospholipid trafficking across the bacterial envelope to maintain outer membrane integrity. MlaB, a STAS domain protein, binds the ABC nucleotide binding domain, MlaF, and is required for its stability. Our structure also implicates a unique C-terminal tail of MlaF in self-dimerization. Both the C-terminal tail of MlaF and the interaction with MlaB are required for the proper assembly of the MlaFEDB complex and its function in cells. This work leads to a new model for how an important bacterial lipid transporter may be regulated by small proteins, and raises the possibility that similar regulatory mechanisms may exist more broadly across the ABC transporter family.
Data availability
The structure factors and coordinates for crystal structures were deposited in the Protein Data Bank with accession codes 6XGY (dimeric MlaFB with ADP+Mg) and 6XGZ (monomeric MlaFB in apo state). Plasmids generated in this study have been deposited in Addgene. All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
American Heart Association (20POST35210202)
- Georgia L Isom
National Institutes of Health (T32 GM088118)
- Mark R MacRae
National Institutes of Health (R35GM128777)
- Damian C Ekiert
Damon Runyon Cancer Research Foundation (DFS‐20‐16)
- Gira Bhabha
National Institutes of Health (R00GM112982)
- Gira Bhabha
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- László Csanády, Semmelweis University, Hungary
Version history
- Received: June 15, 2020
- Accepted: June 24, 2020
- Accepted Manuscript published: June 30, 2020 (version 1)
- Version of Record published: July 17, 2020 (version 2)
Copyright
© 2020, Kolich 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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